A single dose of 5500 T. retortaeformis infective larvae generated a strong inflammatory response as shown by an early increase in IFN-γ and tissue damage in the duodenum of infected rabbits. At 3 days post-infection, IL-4 expression probably contributed to the production of serum and mucus IgA and IgG, and facilitated parasite removal from the four sections of the small intestine. The mechanisms involved in

the early IFN-γ activation are still unknown. One possibility is that the nematode up-regulated the expression of a Th1 phenotype to avoid the rapid expulsion. Alternatively, IFN-γ is produced by the host as a response to tissue damage and the possible bacterial/micro-flora infiltration into the mucosa tissue. In this respect, a pilot analysis of cytokine expression (IFN-γ, IL-4 and IL-10) PLX 4720 in nonre-stimulated spleen of infected rabbits at 7 days post-infection found no evidence of increased IFN-γ expression, supporting the hypothesis of a host-driven response to tissue damage. The relatively rapid activation of a Th2 phenotype

in the presence of IFN-γ indicates that both immune phenotypes can operate and target different components of the infection process, namely, nematode expulsion and tissue repair. Antibodies quickly developed and remained relatively high throughout the infection for IgG but not IgA, suggesting long-term persistence of both systemic and local IgG and some level of protection to reinfections. We found evidence of antibody cross-reactivity BIBW2992 cell line to the somatic products of adult and L3 stages. However, the significant increase in serum antibody in infected hosts at 1 week post-infection was clearly a response to the larval stage L3 and probably L4, as adults are present by 10 days post-challenge (25). A strong but short-lived systemic eosinophilia and blood cells recruitment to the site of infection appeared to develop as a response to the infection dose and contributed to nematode reduction, as observed in other studies of gastrointestinal helminth

infections (32). Parasites were consistently eliminated from the relatively less colonized third and fourth sections of the small intestine, supporting the hypothesis that worm clearance was mainly driven by immune-mediated processes Tenofovir molecular weight rather than parasite density-dependent mechanisms. As a consequence of the T. retortaeformis infection, rabbits developed anaemia but regularly gained body mass with the ad lib food regime. Our findings on the spatio-temporal distribution of T. retortaeformis along the small intestine and the evidence of tissue damage and cells infiltration were consistent with previous studies of rabbits infected with different numbers of larvae (17,24). Our results were also in line with a prompt Th2 immune response to a gastrointestinal helminth infection as highlighted by the relatively rapid IgA, IgG and eosinophil recruitment, probably IL-4 and IL-5 mediated.

In our case, the NFTs were seen in the periaqueductal gray matter, oculomotor nuclei and trochlear nuclei.

We could not know why both Orrell’s case and our case had NFTs, deviating from other FALS cases. In both cases, the distribution of NFTs was different from that in Alzheimer’s disease or other degenerative diseases. If we consider the fact that both cases had NFTs, mainly in the brain stem, the I113T mutation itself might be involved in the appearance of NFTs. As Orrell’s case and ours were so different in terms of disease duration, the timing of the appearance of NFTs would not seem to depend on the disease duration. In our present case Ulixertinib of the I113T mutation, we observed CIs and LBHIs, as well as NFTs. We examined these inclusions immunohistochemically in detail. However, clinicopathological studies including gene analysis and immunohistochemical Akt inhibitor examinations of additional ALS cases are essential. The authors have no conflicts of interest to disclose. “
“Spontaneous intracerebral hemorrhage (ICH) is a devastating cause of morbidity and mortality. Intraparenchymal hematomas are often surgically evacuated. This generates fragments of perihematoma brain tissue that may elucidate their etiology.

The goal of this study is to analyze the value of these specimens in providing a possible etiology for spontaneous ICH as well as the utility of using immunohistochemical markers to identify amyloid angiopathy. Surgically resected hematomas from 20 individuals with spontaneous ICH were examined with light microscopy. Hemorrhage locations included 11 lobar and nine basal ganglia hemorrhages. Aβ immunohistochemistry and Congo red stains were used to confirm the presence of amyloid angiopathy, when this was suspected. Evidence of cerebral amyloid angiopathy (CAA) was observed in eight of the 20 specimens, each of which came from lobar locations. Immunohistochemistry confirmed CAA in the brain fragments from these eight individuals. Patients with

immunohistochemically confirmed CAA were older than patients without CAA, and more likely to have lobar hemorrhages (OR 3.0 and PRKACG 3.7, respectively). Evidence of CAA was not found in any of the basal ganglia specimens. One specimen showed evidence of CAA-associated angiitis, with formation of a microaneurysm in an inflamed segment of a CAA-affected arteriole, surrounded by acute hemorrhage. In another specimen, Aβ immunohistochemistry showed the presence of senile plaques suggesting concomitant Alzheimer’s disease (AD) changes. Surgically evacuated hematomas from patients with spontaneous ICH should be carefully examined, paying special attention to any fragments of included brain parenchyma. These fragments can provide evidence of the etiology of the hemorrhage. Markers such as Aβ 1–40 can help to identify underlying CAA, and should be utilized when microangiopathy is suspected.

8 T-cell differentiation occurs by a complex transcriptional programme initiated by TCR and environmental signals but it is also accompanied by epigenetic changes at specific loci.9 We first review the transcription factors that are activated downstream of TCR signalling and then explore certain principles that might operate in regulating them. Signalling through the TCR activates at least three families of transcription factors: nuclear factor of activated T cells (NFAT), activating protein 1 (AP-1) and nuclear factor-κB (NF-κB) (see Fig. 1). Gene expression Selleckchem GW-572016 by these transcription factors is not restricted to

T cells but rather is found in almost every cell type in the body. As a result, extensive biochemical analysis has been performed over the years describing

the network of interacting proteins that activate them. We will briefly review the regulation of these factors in T cells. The NFAT family consists of five members: NFAT1 (NFATp or NFAT c2), NFAT2 (NFATc or NFATc1), NFAT3 (NFATc4), NFAT4 (NFATc3) and NFAT5; NFAT3 is not expressed in immune cells. All NFAT proteins contain a conserved Rel homology domain (regulatory domain) and an NFAT homology domain (DNA-binding domain). All except NFAT5 are regulated by calcium.10 NFAT is a transcription factor that is normally resident in the cytoplasm and is de-phosphorylated by a calcium-dependent phosphatase, calcineurin. This de-phosphorylation activates it and causes its translocation into the nucleus.11 Nuclear export of NFAT is mediated by phosphorylation. Glycogen www.selleckchem.com/screening/stem-cell-compound-library.html synthase kinase 3 (GSK-3) is known to phosphorylate conserved serine residues necessary for nuclear export.12 In peripheral lymphocytes, antigen receptor signalling leads to the rapid inactivation of GSK-3. Activators of PKA suppress interleukin-2 (IL-2) production and T-cell activation, consistent with the possibility that NFAT is a substrate for protein kinase A (PKA).12 NFAT4 is known to be negatively regulated through phosphorylation by casein kinase 1 in the cytoplasm.13 Another mechanism of negative regulation of NFAT involves calcipressin, a target of NFAT that

binds to and inhibits calcineurin.10 Members of the homer family have been shown to bind to NFAT and compete with calcineurin, hence negatively regulating NFAT IKBKE activation.14 Nuclear retention of NFAT can also be achieved by sumoylation, adding another level of complexity in its regulation.15 Unlike NFATc2, which is constitutively transcribed in T cells, transcription of the NFATc1 gene in effector T cells is strongly induced within 3–4 hr of TCR and co-receptor stimulation.16 Members of the NFAT family are redundant, as the mice lacking individual NFAT proteins show mild alterations in immune function whereas more severe defects are observed when more than one member is knocked out.10 NFAT plays a crucial role in T-cell differentiation.

Kidney function remained stable in patients treated with valsartan combined with probucol or valsartan alone. However, the long-term effect needs further investigation. We are deeply grateful to all the patients who donated blood. This work was supported by grants from Guangzhou people’s livelihood science and technology major projects of Guangdong (2012Y2-00028); Guangdong science and technology plan (2012B031800016). Clinical Trial Registration: A Study of the Antioxidant Probucol Combined

With Valsartan in Patients With IgA Nephropathy (NCT00426348). “
“Date written: June 2007 Final submission: October 2008 No recommendations possible based on Level I or II evidence (Suggestions are based on Level III and IV evidence) A formal psychosocial assessment should be a mandatory CH5424802 purchase part of the pre-transplant workup process. Living kidney donors should undergo psychosocial assessment and have access to psychosocial care before and after the transplant surgery. Living kidney

donor transplantation leads to better outcomes for the transplant recipient; however, there is increasing concern about the safety and wellbeing of live kidney donors.1 Live donors are not only at risk of physical adverse events including infection and loss of renal Selleckchem Lenvatinib function in the remaining kidney but they may also experience psychosocial problems including anxiety, depression, regret and financial hardship.2,3 The psychosocial evaluation of donors (pre- and post-transplant) is widely advocated;4 however, there is a paucity of data on the process and content of psychosocial evaluations. For example, there are tuclazepam no set standards regarding who should conduct psychosocial evaluations (physician, psychiatrist, psychologist, medical social worker), whether evaluations should be mandatory, at what stage of the work-up evaluations should be conducted, at what time interval repeat evaluations should be

performed and what criteria need to be met. A limited number of studies and evaluation tools have suggested that the live donor psychosocial evaluation should include an assessment of: the donor’s ability to give informed consent, donor motivation, relationship between donor and recipient, donor/spouse agreement, information needs, mental status, coping and personality style, emotional and behavioural issues that may impact on donation, and social and financial support.4–7 The objective of this guideline is to assess and summarize the evidence on psychosocial care for living donors. Databases searched: MeSH terms and text words for kidney transplantation were combined with MeSH terms and text words for living donors and MeSH terms and text words for social psychology and support. The search was conducted in Medline (1955 to September Week 1, 2006). Date of searches: 9 September 2006.

Autoimmune check details responses trigger demyelination in the CNS. Important examples of this phenomenon include multiple sclerosis (MS), neuromyelitis optica (NMO) and acute disseminated encephalomyelitis (ADEM). Although the direct role of inflammasomes in those diseases remains largely unknown, the use of experimental autoimmune encephalomyelitis (EAE), an animal model of MS, has made the impact of inflammasomes on CNS autoimmune demyelinating

diseases more apparent. Inflammasomes process interleukin-1β (IL-1β) and IL-18 maturation in myeloid cells, such as macrophages and dendritic cells (DCs); and, the basic biological function of inflammasomes is shared between humans and mice. Inflammasome is a multi-protein complex. Formation of the complex leads to pro-caspase-1 self-cleavage and generates active caspase-1, which processes pro-IL-1β and pro-IL-18 to mature IL-1β and IL-18, respectively, and induces cell death termed “pyroptosis”.

Pyroptosis is distinguished from apoptosis Selleck BGB324 and necrosis by cytoplasmic swelling and activation of caspase-1. Early plasma membrane rupture by pyroptosis[1-3] leads to the release of mature IL-1β and IL-18 and other cytoplasmic contents to the extracellular space.[4] Inflammasomes are known to sense and are activated by pathogen-associated molecular patterns (PAMPs), as well as damage-associated molecular patterns (DAMPs). The Nod-like receptor (NLR) family pyrin domain containing 3 (NLRP3, also known as NALP3 or CIAS1) inflammasome, is currently the most fully characterized inflammasome. It is known to sense bacteria, fungi, extracellular ATP, amyloid β and uric acid,[5-8] as well as various environmental irritants, such as silica, asbestos and alum.[7, 9-11] In addition to NLRP3, other NLR family members, including NLRP1, NLRC4 (IPAF) and AIM2, are known to have clear physiological functions in vivo upon inflammasome formation;[12] however, their involvement in CNS autoimmunity is not clear. Many excellent

reviews are available Cobimetinib datasheet in the literature that provide information on the detailed functions and structure of inflammasomes. Further discussion on inflammasomes themselves is therefore spared here. Rather, we look to briefly mention several basic features of inflammasomes below to provide a foundation for later discussions in this review, and to highlight selected recent findings considered crucial to the further study of inflammasomes in CNS autoimmune demyelinating diseases. The multi-protein complex of the NLRP3 inflammasome is comprised of three different proteins; NLRP3, ASC (apoptosis-associated speck like protein containing a caspase recruitment domain), and pro-caspase-1. Other types of inflammasomes have different compositions of proteins, but all have pro-caspase-1; therefore, the release of IL-1β and IL-18 from cells is a major common outcome by all inflammasomes.

There is extensive evidence suggesting that M. tuberculosis strongly modulates the immune response, both innate and adaptive, to infection, with HM781-36B research buy an important role for regulatory T (Treg) cells [2]. In mice, M. tuberculosis infection triggers antigen-specific CD4+ Treg cells that delay the priming of effector CD4+ and CD8+ T cells in the pulmonary LNs [3], suppressing the development of CD4+ T helper-1 (Th1) responses

that are essential for protective immunity [4]. Thus, these CD4+ Treg cells delay the adequate clearance of the pathogen [5] and promote persisting infection. M. tuberculosis — as well as Mycobacterium bovis bacillus Calmette-Guérin (BCG) — have been found to induce CD4+ click here and CD8+ Treg cells in humans [6-8]. CD4+ and CD8+ Treg cells are enriched in disseminating lepromatous leprosy lesions, and are capable of suppressing CD4+ Th1 responses [9, 10]. Naïve CD8+CD25− T cells can differentiate into CD8+CD25+ Treg cells following antigen encounter [11]. In M. tuberculosis infected macaques, IL-2-expanded CD8+CD25+Foxp3+ Treg cells were found to be present alongside CD4+ effector T cells in vivo, both in the peripheral blood and in the lungs [12]. In human Mycobacterium-infected LNs and blood, a CD8+ Treg subset was found expressing lymphocyte activation gene-3 (LAG-3) and CC chemokine ligand 4 (CCL4, macrophage inflammatory protein-1β). These CD8+LAG-3+CCL4+ T cells could be isolated from

BCG-stimulated PBMCs, co-expressed classical Treg markers CD25 and Foxp3, and were able to inhibit Th1 effector cell responses. This could be attributed in part to the secretion of CCL4, which reduced Ca2+ flux early after T-cell receptor triggering [8]. Furthermore, a subset of these CD8+CD25+LAG-3+ T cells may be restricted by the HLA class Ib molecule HLA-E, a nonclassical HLA class I family member. These latter T cells displayed cytotoxic as well as regulatory activity in vitro, lysing target cells only in the presence of specific

peptide, whereas their regulatory function involved membrane-bound TGF-β [13]. Despite these recent findings, the current knowledge about CD8+ Treg-cell phenotypes and functions is limited and fragmentary when compared with CD4+ Treg cells [6, 14]. CD39 much (E-NTPDase1), the prototype of the mammalian ecto-nucleoside triphosphate diphosphohydrolase family, hydrolyzes pericellular adenosine triphosphate (ATP) to adenosine monophosphate [15]. CD4+ Treg cells can express CD39 and their suppressive function is confined to the CD39+CD25+Foxp3+ subset [16, 17]. Increased in vitro expansion of CD39+ regulatory CD4+ T cells was found after M. tuberculosis specific “region of difference (RD)-1” protein stimulation in patients with active tuberculosis (TB) compared with healthy donors. Moreover, depletion of CD25+CD39+ T cells from PBMCs of TB patients increased M. tuberculosis specific IFN-γ production [18].

As a consequence, LPS-treatment enhanced the migratory activity along a chemokine (CCL21)-gradient in WT, but not in TLR4-deficient BMDCs suggesting that the LPS/TLR4-induced Adriamycin swelling response facilitates DC migration. Moreover, the role of calcium-activated potassium

channels (KCa3.1) as putative regulators of immune cell volume regulation and migration was analyzed in LPS-challenged BMDCs. We found that the LPS-induced swelling of KCa3.1-deficient DCs was impaired when compared to WT DCs. Accordingly, the LPS-induced increase in [Ca2+]i detected in WT DCs was reduced in KCa3.1-deficient DCs. Finally, directed migration of LPS-challenged KCa3.1-deficient DCs was low compared to WT DCs indicating that activation of KCa3.1 is involved in LPS-induced DC migration. These findings suggest that both TLR4 and KCa3.1 contribute to the migration of LPS-activated DCs as an important feature of the adaptive immune response. Dendritic cells (DCs) are the most potent antigen-presenting cells that play a key role in regulating T-cell-mediated adaptive immune responses [1]. Immature DCs placed in peripheral tissues act as sensors for microbial pathogens, stress, or inflammatory signals. Uptake of antigens or exposure to inflammatory stimuli MI-503 mouse at peripheral sites causes maturation of DCs including the up-regulation of MHC and co-stimulatory

molecules and the conversion to a migratory phenotype [1]. Migration of DCs to the draining lymph nodes and presentation of the antigen to T cells can initiate a protective immune response or promote regulatory T cell responses that help to maintain tolerance against the antigen [2]. Recognition of LPS, a cell wall component of gram-negative bacteria by DCs is mediated mainly by Toll-like receptor

(TLR) 4 [3, 4]. Binding of LPS to TLR4 causes maturation and migration of DCs [5]. However, the underlying mechanisms of LPS-induced DC migration are not well understood. In DCs stimulated with LPS dissolution of cell adhesion structures in a TLR4-dependent manner has been described [6] suggesting that TLR4 signaling and actin-driven cytoskeletal rearrangement are involved Ribonuclease T1 in LPS-induced DC migration. Additionally, it has been demonstrated that ion channels contribute to the conversion of DCs towards a migratory phenotype [7]. Accordingly, DCs respond to LPS with a fast increase in free cytosolic calcium ions originating from both intracellular and extracellular calcium stores [7]. Moreover, activation of voltage-gated potassium channels (Kv1.3 and Kv1.5) and sustained increase in [Ca2+]i via store-operated calcium channels (ICRAC) have been shown to play an important role for LPS-induced DC maturation and migration [7]. In addition to voltage-gated K+ channels several members of Ca2+-activated K+ channels like BK (KCa1.1), SK3 (KCa2.3), and in particular SK4 (KCa3.1, IK1, KCNN4) are involved in cell migration [8].

In five patients from whom sera prior to PML diagnosis were available, antibody titres increased 5–10 months before PML diagnosis [61]. Methodological issues such as fluctuating serostatus around assay cut-points [52, 61] and false negative rates [60] argue for a refinement of assay procedures with better reproducibility in low-antibody reactivity ranges. Thus, a second-generation enzyme-linked immunosorbent assay (ELISA) with a reported sensitivity of 98% [62] was introduced; however, so far an independent validation is lacking. Using this refined assay, the possible value

of antibody reactivity for PML risk stratification was reported recently EPZ015666 nmr as abstract. Pexidartinib price Whereas increased immunoreactivity to JCV prior to PML would be biologically plausible, more data are needed to corroborate these initial findings. Higher NAT plasma levels have been associated with lower body mass index and a supposedly higher risk for the development of PML, which needs to be further confirmed as a possible biomarker feasible for clinical routine [44]. Host factors promoting PML development include the determination of immunocompetence. It has been shown conclusively that both CD4+ and CD8+

T cells are important in the immune response to JCV and containment of PML [48, 63]. Investigation of the role of CD4+ T cells has demonstrated a lacking or even anti-inflammatory interleukin (IL)-10 response to JCV in a small number of PML patients [64]. Intracellular adenosine triphosphate

(ATP) levels as a functional parameter of T cell function were decreased Dichloromethane dehalogenase in CD4+ T cells both after long-term NAT treatment and PML of different aetiology [65]. However, this assay was confronted with pre-analytical difficulties, so far impeding application in larger validating studies or clinical routine, as shown by analysis of STRATA samples (Natalizumab Re-Initiation of Dosing; ClinicalTrials.gov NCT00297232) that could not confirm ATP decrease in five pre-PML samples [66]. However, heterogeneous intervals of testing before PML onset may have influenced these results. It may be hypothesized that individual courses of ATP levels are more critical than absolute ATP level, and that a critical time-point of ATP decrease before PML onset has to be determined. Recently, a lower proportion of L-selectin-expressing CD4+ T cells was associated with higher PML risk in NAT-treated MS patients (n = 8). Further validation as a potential biomarker for PML risk stratification is warranted [67]. The determination of its biological plausibility remains unclear thus far, as it might express the general activation status of the peripheral immune system or a defective T cell response to JCV infection on different levels [67].

faecalis infection, whereas all of the SCIDbgMN mice inoculated with Mϕs from burned WT mice died after the same infection.

Also, burned CCL2-knockout mice treated with rCCL2 were shown to be susceptible to E. faecalis infection, and M2Mϕs were isolated from these mice 25. In the present study, we tried to protect thermally injured mice orally infected with a lethal dose of E. faecalis by gene therapy utilizing phosphorothioate-CCL2 antisense oligodeoxynucleotides (ODNs). Antisense ODNs, ribozymes and small-interfering RNA have been used for cytokine knockdown therapy 26, 27. As compared with alternative technologies for blockage of CCL2, antisense ODNs have a higher specificity and probability of success 28. The advantage of antisense ODNs designed as phosphorothioates specifically to heterogeneous nuclear RNA or mature mRNA sequences is resistance to degradation by RNases selleck inhibitor 26. Therefore, for the blockage of CCL2 in severely burned mice orally infected with E. faecalis, Dorsomorphin phosphorothioate-CCL2 antisense ODNs were utilized in this study. In our previous studies 23, 24, CCL2 produced in response to burn injury was shown to play a

major role on the M2Mϕ predominance in severely burned mice. Therefore, for the elimination of M2Mϕs; we tried to reduce serum CCL2 levels of severely burned mice by treatment with CCL2 antisense ODNs. Various concentrations of CCL2 antisense ODNs were administered

to mice 2 and 12 h after burn injury. Sera, obtained from these mice 24 h after burn injury, were assayed for CCL2 by ELISA. Serum specimens obtained from normal mice treated with saline and severely burned mice treated with scrambled ODNs were utilized as controls. CCL2 was not detected in the sera of normal mice, whereas the sera of severely burned mice treated with scrambled ODNs contained 1.3 ng/mL of CCL2. However, 77–100% of CCL2 was eliminated from the sera of severely burned mice after treatment with 1 μg/mouse (Fig. 1A) or more (10 and 100 μg/mouse, Fig. 1B) of CCL2 antisense ODNs. These results indicate that the gene therapy utilizing CCL2 antisense ODNs is feasible to decrease CCL2 levels in severely burned mice. The disappearance of MLN-M2Mϕs in severely burned mice treated G protein-coupled receptor kinase with CCL2 antisense ODNs was examined. Severely burned mice were treated twice with 10 μg/mouse of CCL2 antisense ODNs 2 and 12 h after burn injury. Mϕs isolated from mesenteric lymph nodes (MLN-Mϕs) of these mice 1–8 days after burn injury were cultured for 24 h without any stimulation. Culture fluids harvested were assayed for CCL17 as a biomarker of M2Mϕs. The amounts of CCL17 detected in the culture fluids were compared with those of CCL17 that were produced by the same MLN-Mϕs derived from controls (burned mice treated with scrambled ODNs).

Overall, RAS or CPS immunizations resulted in sporozoite-specific IFNγ responses in the liver (P = 0.03) and spleen (P = 0.008). Although not reaching statistical significance, there was a tendency of higher sporozoite-specific IFNγ response by

T cells with memory phenotype (CD44hi) in liver and spleen (Figure 2b) cells from IV immunized compared to ID immunized C57BL/6J mice. Within the T-cell population, similar observations were made for CD8+CD44hi T cells. Furthermore, the levels of CD8+ Tem cells in both IV and ID groups correlated with the IFNγ response in liver (R = 0.63, P = 0.003) and spleen (R = 0.54, P = 0.01). Three weeks after challenge, the observed high levels of liver CD8+ Tem cells (Figure 2c) and increased IFNγ responses (Figure 2d) were sustained in PD0325901 chemical structure IV immunized mice. No data were obtained from ID immunized mice as these did not

survive challenge infection (Table 1). Finally, functionality of RAS- and CPS-induced antibodies was tested in the sporozoite neutralization assay, testing their capacity to invade and subsequently develop in liver cells (24). Sporozoite invasion was strongly reduced in the presence of plasma from both RAS and CPS immunized mice (P ≤ 0.05), with stronger inhibition by IV immunized mice within the RAS group (P < 0.01) (Figure 3). As CPS ID immunized mice showed similar blocking activity compared to IV immunized mice, antibodies may contribute but are by themselves likely not selleck sufficient

to induce complete protection. Our findings show that ID immunization this website with whole live malaria parasites confers a far lower protective efficacy when compared to IV immunization. The reduced protective efficacy clearly associates with a lower number of sporozoites reaching the liver. Lower protective efficacy by ID immunization was observed in both BALB/c and C57BL6/j mice using two independent immunization protocols, that is, sporozoite liver cell invasion only with early developmental arrest (RAS) or full completion of liver maturation and early abrogation of blood-stage multiplication (CPS). Moreover, both RAS and CPS IV immunizations induce higher cellular immune responses compared to ID. Our data confirm the earlier formulated hypothesis by Epstein et al. (18): based on low hepatic immune responses in ID immunized animals and low protection level in a clinical trial, the authors suggest that the degree of parasite liver load following sporozoite administration associates with protective efficacy. However, ID immunization can induce high levels of protection provided that sufficiently high numbers of sporozoites (i.e. 9 × 104P. yoelii) are injected (17). The necessity of high numbers of sporozoites for ID induced protection supports the notion that liver parasite load might be important for protective efficacy of whole sporozoite immunization. ID injection of P.