Both CD4+ and CD8+ T cells can mediate vaccine-induced protection against Coccidioides immitis infection in mice.
To determine which lymphocytes are required for vaccine-induced immunity to coccidioidomycosis, we used a temperature-sensitive mutant of Coccidioides immitis to immunize mice lacking subsets of lymphocytes or specific cytokines and infected the mice 4 weeks later with virulent C. immitis. After 2 weeks, we determined the number of fungi in their lungs and spleens. Vaccine-induced immunity required alpha beta T lymphocytes. beta -2 microglobulin knockout (KO) mice were protected by immunization, and we transferred protection using CD4+ T cells from immunized mice. However, vaccination also protected CD4+ KO mice, which suggests that CD8+ T cells played a role in vaccine-induced immunity, even though they were not required. We adaptively transferred protection using spleen cells from immunized CD4+ KO mice to nonimmune B6 mice, but CD8+ -depleted spleen cells did not protect against infection. Recipients of spleen cells from immunized CD4+ KO mice had 6 times more tumor necrosis factor (TNF)- alpha mRNA in their lungs than did mice that received nonimmune spleen cells, and TNF receptor-1 KO mice were not fully protected by immunization. These results show that both CD4+ and CD8+ T cells can protect against coccidioidomycosis and that TNF- alpha is a necessary component of the acquired immune response.
Fierer
Joshua
J
Department of Medicine, University of California, San Diego School of Medicine, and Research Service, VA San Diego Healthcare System, San Diego, CA 92161, USA. jfierer@ucsd.edu
Waters
Crystal
C
Walls
Lorraine
L
D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D003045:Coccidioides / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D003047:Coccidioidomycosis / Q000276:immunology / Q000517:prevention & control*; D005260:Female; D005657:Fungal Vaccines / Q000276:immunology* / Q000627:therapeutic use; D007111:Immunity, Cellular / Q000235:genetics; D008168:Lung / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D014774:Virulence / Q000235:genetics / Q000276:immunology; D001613:beta 2-Microglobulin / Q000235:genetics
D005657:Fungal Vaccines; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D001613:beta 2-Microglobulin