Cellular immune response and pathology in schistosomiasis

In the present review, some aspects of the cellular response following the murine Schistosoma mansoni infection are described. Due to the peculiar route used by the schistosome to infect its definitive host, the skin appears as a critical site in which the initial events of the host/parasite relationship occur and where the immune response is initiated. Moreover, the induction and the modulation of the granuloma formation, which represent the main aspect of the pathology of this parasitic disease, is under the control of several cellular populations in which CD4 and CD8 T cells play a key role. The cytokines produced in response to the parasite, such as IL7 in the skin and IFN γ in the liver, seem to influence the further development of immunity against Schistosoma mansoni

Schistosomal egg antigen‐responsive CD8 T‐cell population in Schistosoma mansoni‐infected BALB/c mice

We demonstrated here that schistosomal egg antigen (SEA) is able to stimulate an antigen‐specific, cytotoxic CD8+ T‐cell response in mice. Indeed, a single i.p. immunization with SEA resulted in the in vivo induction of significant cytotoxic T lymphocyte (CTL) activity in the spleen within 20 days. Effector cells were classic class I major histocompatibility complex (MHC)‐restricted CD8+ lymphocytes producing interferon‐γ (IFN‐γ) and interleukin‐2 (IL‐2), suggesting a type 1 response to SEA. We therefore investigated the relevance of these observations in the context of the Schistosoma mansoni parasite infection. CTL activity against SEA‐pulsed target cells was evidenced throughout the infection after in vitro stimulation of recovered splenic cells with SEA demonstrating that SEA‐specific CD8+ T cells with cytotoxic potentialities are present during infection. This activity was strongly increased after immunization of mice with SEA like the production of IFN‐γ in the sera. A marked reduction in the number of granulomas and of fibrosis with the presence of cells producing IFN‐γ in the liver was also observed leading to the survival of SEA‐immunized mice

[Regulatory T-cells and hepatocellular carcinoma: implication of the regulatory T lymphocytes in the control of the immune response]

International audienceHepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and also the third most common cause of cancer-related death. HCC arises most frequently in males with cirrhosis, which is most often a consequence of chronic hepatitis infection (HBV and HCV) or alcohol abuse. To date, the only effective approaches for patients with HCC are resection or liver transplantation. Immunological mechanisms are important in the surveillance of malignancy and control of tumor progression. Tumor-infiltrating lymphocytes (TILs) have been described in HCC, and extensive infiltration has been associated with reduced tumor recurrence following resection. However continued tumor-growth, despite the presence of a lymphocytic infiltration, including tumor-specific T-cells within and surrounding tumors, suggests a failure of immune control. Although, many mechanisms have been proposed for this attenuated immune response, it becomes evident that direct suppression of effector cells, supported by regulatory T-cells could play a pivotal role in the suppression of immune response to tumors. Initially described in context of immune disorders such as inflammatory autoimmune pathologies, regulatory T lymphocytes are characterized by their capacity to inhibit T helper response. To date, several regulatory T-cells are described, however CD4+CD25+ regulatory T-cells and Tr1 subpopulations remain best characterized. Currently, there is no evidence for direct implication of CD4+CD25+ regulatory T-cells in the malignancy and control of HCC progression. However, recent studies showed that both regulatory T-cells subpopulations and particularly Tr1 have been implicated in the modulation of the immune response during HCV chronic infection, supporting HCC progression

Rôle des Lymphocytes T régulateurs dans la progression de la fibrose hépatique associée à l'infection par le VHC.

Hepatitis C virus (HCV) becomes chronic in about 85 % of infected individuals, whereas only 15 % of infected people clear spontaneously the virus. The progression of hepatitis C to chronic status is associated to a profound down-regulation of CD4 and CD8 multispecific immune response. This immune defect may participate to the immune tolerance of VHC and consequently to its persistence. Recent findings indicate that T regulatory cells as Tr1 play an inhibitory role on T helper responses notably in the context of auto-immune or inflammatory disorders. The existence of immunosuppressive mechanisms supported by Tr1 lymphocytes and their IL-10 production represent an attractive hypothesis. We have previously evaluated the existence of regulatory T cells (Tr1) via high production of IL-10, in liver biopsies of three well-defined cohorts of HCV-1b infected patients. To this purpose, we compared liver biopsies of chronically infected patients including patients without liver lesions, with cirrhosis and with hepatocellular carcinoma (HCC). Using quantitative real time PCR, the results obtained demonstrate, an increased expression of interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta)_, in liver biopsies with more severe fibrosis. This observation was correlated with an increased expression during the pathogenesis progression, of the three specific markers of the Tr1 cells sub-population, recently described and confirming the Tr1 phenotype. Evidence of regulatory T cells installation in the liver of chronically infected patient and increased frequency in cirrhosis and HCC suggest a main role of these cells in the aggravation of the liver pathology. This study should bring insight of T regulatory cell implications in VHC persistence and in the pathology progression.English AbstractJournal Articleinfo:eu-repo/semantics/publishe