Cell populations in the lesion of human cutaneous leishmaniasis: A light microscopical, immunohistochemical and ultrastructural study

Abstract

To characterize the in situ cellular immune response in localized cutaneous leishmaniasis (LCL), the authors studied frozen skin biopsies from 50 patients with LCL due to Leishmania braziliensis guyanensis. A panel of 31 monoclonal antibodies was used, which defined the number and distribution of inflammatory cell subsets. Skin inflammatory infiltrates were composed of T cells (with a local CD4/CD8 ratio of 1.05 +/- 0.7 vs 1.48 +/- 0.3 in peripheral blood), macrophages and a smaller number of B cells, natural killer cells and granulocytes. Most of the T cells expressed activation markers (interleukin-2 and transferrin receptors, HLA-DR+) and an increase in T-cell-receptor gamma delta expression was noted. Analysis of the CD4+ subpopulations with newly available reagents showed that helper T cells (CD4+CD45RO+) exceeded the suppressor/inducer subset (CD4+CD45RA+) by 1.4:1. There were no differences between local immune variables from patients with primary infection (45 patients) and those with recurrence (5). In 7 patients, biopsies were analysed before and 1 month after specific treatment, and did not show significant differences except for a small increase of dermal CD1a+ (Langerhans) cells/mm2. The observed pattern of cellular skin infiltration suggests an immune-mediated tissue injury including T-cell-mediated cytotoxicity and delayed hypersensitivity reactions in addition to direct parasitic action.

CD8+ T Cells Are Required for Primary Immunity in C57BL/6 Mice Following Low-Dose, Intradermal Challenge withLeishmania major

“…Our conclusions regarding the role of CD8 ϩ T cells in pathogenesis and in the control of primary infection by L. major are consistent with clinical studies reporting high numbers of intralesional CD4 ϩ and CD8 ϩ T cells present during the acute stage of lesion formation and during the healing process (45)(46)(47)(48)(49)(50). The finding that CD8 ϩ T cells are essential for development of naturally acquired immunity to primary infection has important implications regarding vaccine design.…”

LACK-Specific CD4 + T Cells That Induce Gamma Interferon Production in Patients with Localized Cutaneous Leishmaniasis during an Early Stage of Infection

“…ϩ T cells in lesions due to L. guyanensis (9). We are currently analyzing the expression of molecules, such as cutaneous lymphocyte antigen (11), on skin-homing T cells to analyze the homing of the LACK-specific CD4 ϩ T cells.…”

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

“…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).…”