B-cell infiltration and frequency of cytokine producing cells differ between localized and disseminated human cutaneous leishmaniases

Abstract

Biopsies from human localized cutaneous lesions (LCL n = 7) or disseminated lesions (DL n = 8) cases were characterized according to cellular infiltration, frequency of cytokine (IFN-γ, TNF-α) Cutaneous leishmaniasis is a worldwide disease with severe deformating potential in new world. It affects preferentially young economically active patients representing a large burden to the public health system in developing countries. Protection against all forms of leishmaniasis is dependent on cell-mediated immunity (CMI), but the contribution of some cells and cytokines in human disease deserves further scrutiny.CD8 + T cells have been implicated in protection (Muller et al. 1991) being high IFN-γ producers in a murine model of leishmaniasis (Chan 1993). Their role seems to be more in the secondary than in the primary immune response (Muller et al. 1993(Muller et al. , 1994. On the other hand, the course of leishmaniasis in mice lacking beta 2-microglobulin (beta 2-m) gene did not differ from their wild-type counterparts (Overath & Harbecke 1993, Wang et al. 1993, Huber et al. 1998) lessening a role of antigen presentation by major histocompatibility complex class I (MHC I) molecules. In man, a higher percentage of CD8 + over CD4 + T cells was found in mucocutaneous leishmaniasis (MCL) lesions (Castes & Tapia 1998), compared to localized cutaneous lesions (LCL), although similar distributions of CD4 + and CD8 + in LCL have been reported (Barral et al. 1987, Esterre et al. 1992, Lima et al. 1994. The presence of cytotoxic CD8 + T cells has been reported in peripheral blood of MCL but not in LCL patients (Brodskyn et al. 1997). Expansion of CD8 + T cells occurs in the peripheral blood of individuals vaccinated against leishmaniasis (Mendonça et al. 1995, Gurunathan et al. 2000. Especially, the percentage of activated CD8 + T cells was higher in fast responding than in slow responding volunteers to vaccination (Pompeu et al. 2001).The role of B cells in leishmaniasis is also not clear. High antibody levels are present in the more severe clinical form of the cutaneous disease, namely diffuse cutaneous leishmaniasis (DCL) (Schurr et al. 1986, Mengistu et al. 1990), but B cell depletion does not alter the susceptibility or resistance pattern to Leishmania infection in mice (Babai et al. 1999, Brown & Reiner 1999. It seems that B cells are important to induce anti-Leishmania CD4 + Th1 cells and DTH reaction, in the resistant mouse strain, and take part in the humoral response development in susceptible animals (Scott & Farrell 1982, Scott et al. 1986).Predominance of Th1 cytokines like IFN-γ, IL-12, IL-2 and TNF-α over Th2 cytokines, IL-4, IL-5 IL-10 and TGF-β, is correlated in mice to the resistance profile against Leishmania infection (Belosevic et al. 1989, Chatelain et al. 1992, Lezama-Davila et al. 1992, Barral et al. 1993. Imunological studies in humans demonstrated a combination of Th1 and Th2 cytokines with predominance of Th1 in MCL, Th2 predominate in DCL and predominance of Th1 profile in LCL patients , Castes et...

Clinical and immunopathological spectrum of American cutaneous leishmaniasis with special reference to the disease in Amazonian Brazil: a review

“…However, although LCL is regarded as having a well balanced cellular immune response with a very high level of resistence to infection (CD8+>CD4+ and Th1>Th2), there is not yet a general agreement as to which type of T cell (either CD4+ or CD8+) is predominant in the infiltrate of the cutaneous lesions of patients. For example, Barral et al (1987), Pirmez et al (1990), and Esterre et al (1992) found a higher predominance of CD4+ T cells but, in contrast, Modlin et al (1985), Martinez-Arends et al (1991), Isaza et al (1996) and Vieira et al (2002) showed that CD8+ T cells are the most frequent type of lymphocyte. In Amazonian Brazil, however, our results of immunocytochemistry analysis (Fig.…”

“…In general, it has been considered that LCL patients present an adequate cell-mediated immunity with a predominance of CD4+ Th1 immune response (Cáceres-Dittmar et al 1993, Pirmez et al 1993. There is not yet, however, a consensus of opinion as to which type of memory T cell (either CD4+ or CD8+ subsets) is the more prevalent in the infiltrate of lesions (Modlin et al 1985, Barral et al 1987, Pirmez et al 1990, Martinez-Arends et al 1991, Esterre et al 1992, Isaza et al 1996, Vieira et al 2002. In view of the complex etiology of ACL in Amazonian Brazil, the cell-mediated immunity of the disease needs to be studied not only in terms of the clinical features of the disease but also with regards to the specific leishmanial parasite involved.…”

Inflammation in disseminated lesions: an analysis of CD4+, CD20+, CD68+, CD31+ and vW+ cells in non-ulcerated lesions of disseminated leishmaniasis

“…CD4 + T-cells are well implicated in the immune response against Leishmania and are the main source of IFN-g in CL (Faria et al 2009). With the evolution of the disease, a higher number of CD4 + T-cells become correlated with the presence of IFN-g (Vieira et al 2002, Faria et al 2009). As the disease evolves, a growing number of CD4 + T-cells produce IFN-g. Our analysis of CD4 + T-cells is consistent with a mechanism of inflammation progression in which CD4…”

“…Th1 lymphocytes generate interleukin (IL)-10, which may down-regulate IFN-g (Wana- sen et al 2008). Great expression of IL-10 at inflamed sites may regulate the host response to tissue damage and lead to posterior healing (Vieira et al 2002, Wanasen et al 2008). …”

Dynamics of Capillaria-hepatica-induced hepatic septal fibrosis in rats

“…For morphometric measurements, a total sectional area of 5.0 x 10mm 2 per case was evaluated. Automatic morphometric analysis was performed in a similar manner to that previously described 10,11 . Briefly, the actin-positive cells present within the sectional area were all counted.…”