Elimination of CD4+ suppressor T cells from susceptible BALB/c mice releases CD8+ T lymphocytes to mediate protective immunity against Leishmania.

Abstract

This study examined the capacity of BALB/c mice that had been depleted of T cell subpopulations to generate a protective immune response to Leishmania major. Thymectomized mice were depleted of either L3T4+ (CD4+) T lymphocytes, Ly2+ (CD8+) T lymphocytes, or both, by treatment with appropriate mAbs. It was found that susceptible mice were rendered resistant to Leishmania by an intravenous infusion of anti-L3T4 mAb. These mice generated an immune response that destroyed the parasite in the primary lesion and in visceral metastatic foci. CD4+ cell-depleted mice also acquired a capacity to mount a sustained delayed-type hypersensitivity (DTH) response to parasite antigens, indicating that DTH, per se, is not a disease-promoting mechanism in the susceptible murine host as has been suggested. Depleting BALB/c mice of CD8+, as well as CD4+ T cells, left them highly susceptible to Leishmania infection, thereby indicating that CD8+ lymphocytes are key protective cells. Our results can be interpreted as showing that the susceptibility of BALB/c mice is due to the generation of CD4+ cells that suppress either the generation or expression of CD8+ T cell-mediated antiLeishmania immunity.

Differences in Gamma Interferon Production In Vitro Predict the Pace of the In Vivo Response toLeishmania amazonensisin Healthy Volunteers

“…Natural killer cells may be a very important source of IFN-␥ in this situation. While previous reports have shown that CD8 ϩ T cells may not be essential for primary immunity (17), there have been several studies which have shown that CD8 ϩ T cells do have a role in secondary responses (24,25,34). LACK DNA induces antigen-specific CD8…”

Perforin and Gamma Interferon Are Critical CD8+T-Cell-Mediated Responses in Vaccine-Induced Immunity againstLeishmania amazonensisInfection

“…The course of infection in nonvaccinated, resistant mice depleted of CD4 ϩ T cells and challenged with L. major was profound, as these mice were rendered incapable of resolving infection (63). Interestingly, depletion of CD4 ϩ T cells from susceptible BALB/c mice resulted in the control of the infection, which was reversed with depletion of CD8 ϩ T cells (22,43). However, studies that have assessed the role of CD8 ϩ T cells in the control of infection in naïve (nonvaccinated) mice have produced mixed results (7,43,63).…”

Immunologic patterns associated with cure in human American cutaneous leishmaniasis

“…These cytokines are able to inhibit the differentiation of Th1 CD4 + lymphocytes and the production of IFN-γ and TNF (8,11,12). CD8 + T lymphocytes also appear to be important in the immunologic mechanisms responsible for cure of murine leishmaniasis caused by L. major, L. amazonensis, and L. donovani (13)(14)(15). Activated antigen-specific CD8 + T cells have been shown to produce IFN-γ and can have a cytolytic effect on parasitized macrophages (16,17).…”