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 1

Antifungal memory CD8+ T cells develop in the absence of CD4+ T cell help.

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Antifungal memory CD8+ T cells develop in the absence of CD4+ T cell hel...
Cohorts of C57BL/6 (7 to 8 weeks old) mice were vaccinated s.c. with live attenuated yeast of B. dermatitis (105 CFU). After 2 weeks, mice were boosted and rested from 2 weeks (0 months) to 6 months. (A) Ten weeks after vaccination, DLNs were collected from vaccinated CD4+ T cell–sufficient (CD4+) and CD4+ T cell–depleted (CD4–) mice. DLNs cells were surface stained with antibodies against CD44, CD27, CD127, and CD62L and with anti-CD8 antibody. Cells were analyzed by flow cytometry. *P < 0.05. After indicated rest periods, mice were challenged i.t. with a lethal dose of WT B. dermatitidis. Lungs were harvested 4 days later for analysis. Total numbers of CD8+ T cells (B) and activated (CD44hi) CD8+ T cells (C) were quantitated by flow cytometry after surface staining with anti-CD8 and anti-CD44 antibodies. Cells were also surface stained with antibodies against CD62L, CD127, CD122, and CD27. Percentages of CD44hiCD8+ T cells expressing different surface markers were quantitated by flow cytometry and are shown for cells recruited to the lungs after mice were rested for 6 months after vaccination (D). *P ≤ 0.05, vaccinated (vac) versus unvaccinated (unvac) mice; †P ≤ 0.05, CD4+ T cell–depleted versus CD4+ T cell–sufficient mice (B–D). Error bars represent mean ± SD.