Elimination of CD4+ suppressor T cells from susceptible BALB/c mice releases CD8+ T lymphocytes to mediate protective immunity against Leishmania.
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.
Hill
J O
JO
Trudeau Institute, Saranac Lake, New York 12983.
Awwad
M
M
North
R J
RJ
D000818:Animals; D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D016827:CD8 Antigens; D006968:Hypersensitivity, Delayed; D007116:Immunization, Passive; D007700:Kinetics; D007891:Leishmania / Q000276:immunology*; D007896:Leishmaniasis / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D016827:CD8 Antigens