Depletion of murine CD8+ T cells in vivo decreases pulmonary clearance of a moderately virulent strain of Cryptococcus neoformans.
Host defense mechanisms to the important fungal pathogen Cryptococcus neoformans are complex and incompletely understood. From in vitro studies, we could expect CD8+ T cells to have the potential for both protective and suppressive effects on defense against cryptococci. The current study used the technique of in vivo subset depletion to determine the net effect of CD8+ T cells during actual infection. Mice depleted of CD8+ T cells by monoclonal antibody (YTS 169.4) injections were infected with the moderately virulent cryptococcal strain 613D by the intratracheal route, which mimics natural pulmonary infection. To ensure adequacy of depletion, T cell subsets were enumerated by flow cytometry in blood, spleen, lymph node, and lung. Specific elements of host defense were measured by clearance of cryptococci in vivo and by the response to cryptococcal antigens, both in vivo by delayed-type hypersensitivity (DTH) and in vitro by lymphocyte proliferation. We found that depletion of CD8+ T cells decreased pulmonary clearance of C. neoformans. CD8 depletion abrogated DTH without affecting antigen recognition or lymphocyte proliferation in vitro. These data demonstrate that the net effect of CD8+ T cells to a moderately virulent strain of C. neoformans is to enhance rather than suppresses host defenses. Abrogation of DTH suggests that CD8+ T cells contribute to the protective immunologic response to C. neoformans. It is possible that in hosts deficient in CD4 cells, such as patients with AIDS, the protective effects of CD8+ T cells could be stimulated by selected immunizing epitopes.
Mody
C H
CH
Department of Internal Medicine, University of Calgary, Alberta, Canada.
Chen
G H
GH
Jackson
C
C
Curtis
J L
JL
Toews
G B
GB
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000946:Antigens, Fungal / Q000032:analysis; D001773:Blood Cells / Q000473:pathology; D016827:CD8 Antigens / Q000032:analysis*; D002455:Cell Division; D003453:Cryptococcosis / Q000276:immunology / Q000473:pathology; D003455:Cryptococcus neoformans / Q000472:pathogenicity*; D000939:Epitopes / Q000276:immunology; D005434:Flow Cytometry; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007111:Immunity, Cellular / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000473:pathology / Q000502:physiology*; D008171:Lung Diseases / Q000276:immunology / Q000473:pathology; D008198:Lymph Nodes / Q000473:pathology; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D013154:Spleen / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology* / Q000502:physiology; D014774:Virulence
D000911:Antibodies, Monoclonal; D000946:Antigens, Fungal; D016827:CD8 Antigens; D000939:Epitopes