title: Protective antifungal memory CD8(+) T cells are maintained in the absence of CD4(+) T cell help and cognate antigen in mice.
abstract: Individuals who are immunocompromised, including AIDS patients with few CD4(+) T cells, are at increased risk for opportunistic fungal infections. The incidence of such infections is increasing worldwide, meaning that the need for antifungal vaccines is increasing. Although CD4(+) T cells play a dominant role in resistance to many pathogenic fungal infections, we have previously shown that vaccination can induce protective antifungal CD8(+) T cell immunity in the absence of CD4(+) T cells. However, it has not been determined whether vaccine-induced antifungal CD8(+) T cell memory can be maintained in the absence of CD4(+) T cell help. Here, we have shown in a mouse model of vaccination against blastomycosis that antifungal memory CD8(+) T cells are maintained in the absence of CD4(+) T cells without loss of numbers or function for at least 6 months and that the cells protect against infection. Using a system that enabled us to induce and track antigen-specific, antifungal CD8(+) T cells, we found that such cells were maintained for at least 5 months upon transfer into naive mice lacking both CD4(+) T cells and persistent fungal antigen. Additionally, fungal vaccination induced a profile of transcription factors functionally linked with persistent memory in CD8(+) T cells. Thus, unlike bacteria and viruses, fungi elicit long-term CD8(+) T cell memory that is maintained without CD4(+) T cell help or persistent antigen. This has implications for the development of novel antifungal vaccine strategies effective in immunocompromised patients.
authors.affiliation: Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53706, USA.
authors.forename: Som G
authors.initials: SG
authors.lastname: Nanjappa
authors.forename: Erika
authors.initials: E
authors.lastname: Heninger
authors.forename: Marcel
authors.initials: M
authors.lastname: Wüthrich
authors.forename: Thomas
authors.initials: T
authors.lastname: Sullivan
authors.forename: Bruce
authors.initials: B
authors.lastname: Klein
mesh_terms: D019264:Adoptive Transfer; D000483:Alleles; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology; D000941:Antigens / Q000737:chemistry*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology*; D019496:Cancer Vaccines; D016207:Cytokines / Q000378:metabolism; D000939:Epitopes / Q000737:chemistry; D005434:Flow Cytometry / Q000379:methods; D007107:Immune System; D007156:Immunologic Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D012306:Risk; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D000935:Antifungal Agents; D000941:Antigens; D019496:Cancer Vaccines; D016207:Cytokines; D000939:Epitopes; D014157:Transcription Factors