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.
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
Joshua
J
Fierer
Crystal
C
Waters
Lorraine
L
Walls
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