Protective antifungal memory CD8+ T cells are maintained in the absence of CD4+ T cell help and cognate antigen in mice
Som G. Nanjappa, Erika Heninger, Marcel Wüthrich, Thomas Sullivan, Bruce Klein
Som G. Nanjappa, Erika Heninger, Marcel Wüthrich, Thomas Sullivan, Bruce Klein
View: Text | PDF
Research Article Immunology

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

Som G. Nanjappa, Erika Heninger, Marcel Wüthrich, Thomas Sullivan, Bruce Klein

×

Figure 3

Durable fungal resistance by memory CD8+ T cells in the absence of CD4+ T cell help.

Options: View larger image (or click on image) Download as PowerPoint
Durable fungal resistance by memory CD8+ T cells in the absence of CD4+ ...
Different aged mice were vaccinated and rested for several months as described in Figure 1. Vaccinated mice and unvaccinated controls were challenged i.t. at the same age with a lethal dose of WT B. dermatitidis. When unvaccinated controls were moribund (~3 weeks after infection), lungs were harvested to enumerate fungal CFU. (A) Lung CFU in nondepleted and CD4+ T cell–depleted mice. Median is shown in box and whisker plots. Data are from 10–13 mice/group. (B) Lung CFUs of vaccinated WT and Cd4–/– mice and unvaccinated controls. Median is shown in box and whisker plots. Data are from 9–19 mice/group. *P ≤ 0.05 for vaccinated versus unvaccinated mice.