Protective antifungal memory CD8 ⁺ T cells are maintained in the absence of CD4 ⁺ T cell help and cognate antigen in mice

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.