T-cell subpopulations, expression of interleukin-2 receptor, and production of interleukin-2 and gamma interferon in human American cutaneous leishmaniasis

Abstract

Leukocyte subpopulations, the expression of the interleukin-2 (IL-2) receptor, and the production of IL-2 and gamma interferon (IFN-gamma) were studied in the peripheral blood mononuclear cells of American cutaneous leishmaniasis patients that had been stimulated in vitro with either leishmanial antigen or mitogen (phytohemagglutinin M). The 75 patients examined were classified as having either the localized (LCL; 66 patients), mucocutaneous (MCL; 5 patients), or the rare diffuse (DCL; 4 patients) form of the disease. Patients with DCL, who are characterized by their defective cell-mediated immune response to leishmanial antigen, failed to express the IL-2 receptor and did not produce IFN-gamma when exposed to the antigen but did so when stimulated by phytohemagglutinin M. Both LCL and MCL patients showed strong proliferative responses to leishmanial antigen; these were by far the greatest in MCL patients. Both groups had significantly increased IL-2 receptor expression and IFN-gamma production after exposure to either antigen or mitogen, and these were highest in the MCL patients. Concerning the leukocyte subpopulations evaluated (CD2, CD4, CD8, CD20, MO2), the most significant findings were a decrease of both CD4+ cells and the CD4/CD8 ratio in MCL patients compared with the other groups. Considering IL-2 production, in response to phytohemagglutinin M both MCL and LCL patients showed amounts of IL-2 comparable to those of the controls. Our results help explain the anergy of T cells from DCL patients to leishmanial antigen, which could lead to a defective production of IFN-gamma and possibly contribute to their incapacity to kill the Leishmania parasite. Concerning MCL patients, the significantly increased expression of IL-2 receptor, decreased expression of the CD4 (helper-inducer of suppression) phenotype, and elevated IFV-gamma production might partially explains the state of hypersensitivity and mucosal damage exhibited by these patients.

Cell‐mediated immunity in localized cutaneous leishmaniasis patients before and after treatment with immunotherapy or chemotherapy

“…In these same patients we evaluated some aspects of the cellular immune response. When the whole group of LCL patients was compared before treatment to healthy individuals in terms of mitogen-and antigen-induced proliferative responses and leucocyte subpopulations, the results were similar to those reported previously (Castes et al 1983(Castes et al , 1988. No significant differences were found in the Con-A response, and a significant increase of the lymphoproliferative response to leishmanial antigen was found.…”

“…As previously reported (Castes et al 1988), no significant differences were found for these markers in the patients (CD4 44.0f 1.4%; CD8 26.3 f 1.2%; CD25 4.9f0.7%) when compared to the controls (CD4 44-1 f 1 .O%; CD8 29.9 f 2.0%; CD25 5.5 f 1.2%). Results are means f s.d.…”

“…Details concerning the slide preparation and immunoperoxidase staining are as described previously (Castes et al 1988). The cells examined were either non-stimulated, or stimulated with antigen or mitogen before staining.…”

“…In previous studies (Castes et al 1983, Castes, Agnelli & Rondon 1984, Castes et al 1988 we have evaluated the immune response of LCL patients and demonstrated that they have a variable but positive lymphocyte proliferative response to leishmania1 antigen, as well as showing a significantly increased IL-2 receptor expression and IFN-y production after exposure of their peripheral blood leucocytes (PBL) to either antigen or mitogen.…”

New Zealand black mice are immunologically resistant to high-dose, but not low-dose Leishmania mexicana infection

“…The human pathology associated with infection caused by the protozoan parasite L. mexicana can be manifest in several cutaneous forms, ranging from localized healing lesions to nonhealing relapsing (Chiclero's ulcer) and diffuse disseminating lesions (DCL) (Pearson et al, 1983). In addition, in areas where American cutaneous leishmaniasis (ACL) is endemic, fully symptomatic and cured patients can be encountered alongside individuals with no history of lesion development, all of whom may respond significantly to leishmanial antigens in vitro (Castes et al, 1983(Castes et al, , 1988Dorea et al, 1988).…”