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.