Protective antifungal memory CD8+ T cells are maintained in the absence of CD4+ T cell help and cognate antigen in mice
Som G. Nanjappa, … , Thomas Sullivan, Bruce Klein
Som G. Nanjappa, … , Thomas Sullivan, Bruce Klein
Published February 22, 2012
Citation Information: J Clin Invest. 2012;122(3):987-999. https://doi.org/10.1172/JCI58762.
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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

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Figure 2

Long-term maintenance of func­tional antifungal memory CD8+ T cells without CD4+ T cell help.

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Long-term maintenance of func­tional antifungal memory CD8+ T cells with...
Mice were vaccinated and rested as described in Figure 1. Lungs were harvested 4 days after challenge. Lung CD8+ T cells were restimulated ex vivo with anti-CD3 and anti-CD28 antibodies for 5 hours in the presence of Golgi stop. Cells were first surface stained with anti-CD8 and anti-CD44 antibodies before treating with Fix/Perm buffer (BD Biosciences). Intracellular cytokine staining was done using anti–IFN-γ, anti–IL-17A, and anti–TNF-α. Percentages (A) and total numbers (B) of cytokine-producing CD8+ T cells were enumerated by flow cytometry and are shown in mice that were rested for different intervals after vaccination. *P ≤ 0.05, unvaccinated versus vaccinated mice; †P ≤ 0.05, vaccinated CD4+ T cell–depleted vs. vaccinated CD4+ T cell–sufficient mice. Error bars represent mean ± SD.