Although the ABO blood group of the human host has been reported to influence malarial infection, there have been few clinical observations on this effect. A hospital-based, comparative study was therefore performed to investigate the relationship between blood-group type and severe disease i nPlasmodium falciparum malaria. Overall, 243 cases of malaria (163 uncomplicated and 80 severe) and 65 patients with severe, non-malarial infections were studied. In terms of ABO-blood-group composition, the patients with severe malaria were significantly different from the patients with the uncomplicated disease (P<0.001) and also from a population control described previously (P<0.0001). The patients with uncomplicated malaria or severe but non-malarial disease were, however, similar to the population control. The cases of severe malaria were significantly less likely to be of blood group O (P=0.0003), and significantly more likely to be of group AB (P<0.0001), than the patients with nonsevere malaria. It appears that individuals who are of blood-group O are relatively resistant to the severe disease caused by P. falciparum infection.
SummaryThe percentage of peripheral blood mononuclear cells (PBMC) bearing the CD3 § phenotype and the ot/~ and 3//8 T cell receptors (TCR) in PBMC were examined in Plasmodium vivax malaria patients and convalescents. The cells were labeled with monoclonal antibodies, stained with either fluorescene or phycoerythrin, and examined by ultraviolet (UV) microscopy. A highly significant increase in both the proportion and the absolute numbers of 3//8 T cells (p <0.005 and <0.001, respectively, Student's t test) was observed in nonimmune P. vivax patients during clinical paroxysms compared to nonmalarial controls. These T cells, which normally constitute not more than 3-5% of PBMC, constituted ~<30% of PBMC during paroxysms in these nonimmune patients in whom the clinical symptoms were severe. A less significant increase of 3//8 T cells were also observed in these nonimmune patients during infection, between paroxysms and during convalescence. In contrast, in an age-matched group of semi-immune patients resident in a malaria-endemic region of the country, in whom the clinical disease was comparatively mild, there was no increase in 3//8 T cells either during infection, even during paroxysms, or convalescence.The severity of disease symptoms in patients as measured by a clinical score correlated positively with the proportion of 3//8 T cells in peripheral blood (r = 0.53, p <0.01), the most significant correlation being found between the prevalence and severity of gastrointestinal symptoms, nausea, anorexia, and vomiting, and the proportion of 3//8 T cells (r = 0.49, p = 0.002). These findings suggest that 3//8 T cells have a role to play in the pathogenesis of malaria, possibly in the general constitutional disturbances and particularly in gastrointestinal pathology in malaria.T lymphocytes, which express the CD3 marker and lack CD4 and CD8 markers, have been shown to lack mature messenger (m)RNA for ot and/3 genes and express the y and 8 genes and proteins (1). Such lymphocytes expressing the TCR-3//6 constitute a minor subpopulation in the peripheral blood of adults, and many of them reside in the spleen, and to a lesser extent in the thymus, tonsils (2), and the epithelia of the large intestine (3) and lung (4). The biological role of the cells bearing the TCR-3,/8 is as yet unclear, but there are indications that some 3//8 T cells can mediate cytotoxicity (4). 3'/8 T cells behave like c~/B T cells in that they secrete the lymphokines IL-2, IFN-y, TNF-o~ and ~3, and express cytotoxic activity (5-7).Recent evidence has led to speculation about an involvement of 3//8 T cells in immunity and/or immunopathology in human malaria. The frequency of 3//8 T cells in the peripheral blood of acute Plasmodium falciparum malaria-infected individuals has been shown to increase, and remain elevated for several weeks during convalescence (8). In nonimmune individuals, a vast majority of T cells vigorously proliferating in response to freeze-thawed extracts of P. falciparum blood stage parasites in vitro have been shown to be 3//8 ...
BackgroundAlthough antibody responses to dengue virus (DENV) in naturally infected individuals have been extensively studied, the functionality of DENV specific memory T cell responses in relation to clinical disease severity is incompletely understood.Methodology/Principal findingsUsing ex vivo IFNγ ELISpot assays, and by determining cytokines produced in ELISpot supernatants, we investigated the functionality of DENV-specific memory T cell responses in a large cohort of individuals from Sri Lanka (n=338), who were naturally infected and were either hospitalized due to dengue or had mild or sub clinical dengue infection. We found that T cells of individuals with both past mild or sub clinical dengue infection and who were hospitalized produced multiple cytokines when stimulated with DENV-NS3 peptides. However, while DENV-NS3 specific T cells of those with mild/sub clinical dengue infection were more likely to produce only granzyme B (p=0.02), those who were hospitalized were more likely to produce both TNFα and IFNγ (p=0.03) or TNFα alone.We have also investigated the usefulness of a novel T cell based assay, which can be used to determine the past infecting DENV serotype. 92.4% of DENV seropositive individuals responded to at least one DENV serotype of this assay and none of the seronegatives responded. Individuals who were seronegative, but had received the Japanese encephalitis vaccine too made no responses, suggesting that the peptides used in this assay did not cross react with the Japanese encephalitis virus.Conclusions/significanceThe types of cytokines produced by DENV-specific memory T cells appear to influence the outcome of clinical disease severity. The novel T cell based assay, is likely to be useful in determining the past infecting DENV serotype in immune-epidemiological studies and also in dengue vaccine trials.
Plasma levels of pro-and anti-inflammatory cytokines of Plasmodium falciparum-infected patients with severe malaria (SM; n562) and uncomplicated malaria (UM; n569) from Sri Lanka were assessed. SM patients had significantly higher levels of TNF-alpha (P,0.01), IL-6 (P,0.01), and IL-10 (P,0.05) compared to the UM patients. Plasma IL-2 levels of these patients were undetectable. TNF-alpha levels of a third group of patients with uncomplicated P. falciparum malaria, who were recruited during their fever episodes (UMF; n514) were significantly higher than those of the UM patients (P,0.001) and comparable to SM patients. Plasma IFN-gamma levels of SM patients were higher compared to UM patients, but was not statistically significant. Body temperature in both SM and UMF groups were significantly higher compared to UM group, whereas percentages of parasitemia in all three groups were comparable. Analysis of plasma TNF-alpha levels and the ratio of TNF-alpha/IL-10 in UM (n534) and SM (n534) patients carrying TNF1 and TNF2 allelic types showed that SM patients carrying TNF2 had significantly higher TNFalpha levels as well as TNF-alpha/IL-10 ratio compared to UM patients carrying TNF1, UM patients carrying TNF2 and SM patients carrying TNF1 (P,0.05). These results suggest that the high circulating TNF-alpha levels and the inadequate IL-10 response in the SM patients carrying TNF2 allele could have contributed to the development of severe falciparum malarial disease.
BACKGROUND: Reactivation of the varicella zoster virus (VZV) is more common in patients with malignancies; however, the molecular and cellular mechanisms underlying this susceptibility are unclear. METHODS: Using ex vivo interferon-g ELISpot assays, we set out to analyse VZV-specific immune responses in a large cohort of patients with malignancies. RESULTS: We observed that patients with malignancies had impaired VZV-specific T-cell responses, particularly in those with haematological malignancies and breast carcinoma. Immediate-early protein 63 (IE63)-specific T-cell responses were significantly impaired in those with subclinical VZV re-activation. Malignancy is associated with reactivation of chronic persistent viruses such as varicella zoster virus (VZV) (Whiteside, 2006), causing significant morbidity and mortality (Wade, 2006). Herpes zoster is more common in patients with malignancies (Schmader, 2001;Sorensen et al, 2004) and may lead to severe disease with multi-dermatomal involvement and visceral dissemination, which can be lethal (Gallagher and Merigan, 1979;Onunu and Uhunmwangho, 2004;Hackanson et al, 2005;Graue et al, 2006). However, apart from clinically apparent VZV reactivation, subclinical reactivation has also been reported in both immunocompetent and immunosuppressed individuals (Schunemann et al, 1998;Quinlivan et al, 2007). Although the mechanisms underlying such reactivation are unclear, it is thought that cell-mediated immune responses are vital in controlling VZV replication (Malavige et al, , 2008b.VZV glycoproteins I and E, immediate-early protein 63 (IE63) and four specific CD4 þ T cells have been shown to circulate at persistently high frequencies in the peripheral blood of healthy seropositive donors without a history of reactivation (Jones et al, 2006Malavige et al, 2007Malavige et al, , 2008a. However, VZV-specific T-cell responses have been shown to be lower in elderly individuals and in patients with disease such as systemic lupus erythematosus (Miller, 1980;Levin et al, 2003;Park et al, 2004). As these groups of individuals are at a higher risk of herpes zoster, it seems that VZVspecific T cells are important in preventing virus reactivation. Some important studies conducted earlier have indeed shown that suppression of VZV-specific cellular immunity preceded the occurrence of herpes zoster (Arvin et al, 1978(Arvin et al, , 1980. However, with a more detailed understanding of VZV protein-specific responses, we can now study the mechanisms that are important in preventing virus reactivation. Therefore, we set out to analyse the overall VZV-specific immune responses and the immune responses to VZV IE63 and gE proteins, in a cohort of patients with malignancies to identify the associations with viral reactivation. MATERIALS AND METHODSFresh heparinised venous blood samples were obtained from 106 adult individuals with malignancies (before receiving chemotherapy) who were admitted to the Cancer Institute in Sri Lanka with a past history of primary VZV infection. Samples were also obt...
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