Resistance to Cryptococcus neoformans infection in the absence of CD4+ T cells.
Previous studies of Cryptococcus neoformans infection have revealed a role for CD4+ T cells and CD8+ T cells in anticryptococcal resistance in the lungs, but such a role has been revealed only for CD4+ T cells in the brains of experimentally infected mice. In this study, we found that mice genetically engineered to lack CD4+ T cells could be successfully vaccinated to express resistance to a rechallenge with Cryptococcus neoformans, provided the challenge dose was kept to lower than 1000 organisms per mouse. The challenge infection was uniformly lethal for unvaccinated control mice. Depletion of CD8+ T cells weakened this resistance to re-challenge: both naïve and vaccinated mice that were treated with antibody raised against CD8+ T cells died significantly earlier than did mice that received an irrelevant control antibody. In vitro, purified CD8+ T cells taken from draining lymph nodes of antigen-experienced mice were less efficient than were identically prepared CD4+ T cells at stimulating the cells of a transformed microglial cell line to inhibit C. neoformans proliferation, possibly mirroring the inferiority of CD8+ T-cell-mediated protection observed in vivo. RNase protection assays showed similar IFN-gamma mRNA levels in both lymphocyte subsets. Class II major histocompatibility antigen expression was up-regulated strikingly on microglia cultured with IFN-gamma, but class I expression was less dramatically affected. Therefore microglial cell interaction may be more greatly enhanced with CD4+ cells than with CD8+ cells.
Trudeau Institute, Saranac Lake, New York, USA. kmaguirr@clarkson.edu
Karen
K
Aguirre
Jason
J
Crowe
Amy
A
Haas
Janel
J
Smith
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology*; D001921:Brain / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003453:Cryptococcosis / Q000276:immunology*; D003455:Cryptococcus neoformans / Q000276:immunology* / Q000472:pathogenicity; D007114:Immunization; D007371:Interferon-gamma / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
D000942:Antigens, Bacterial; D007371:Interferon-gamma