Journal
JOURNAL OF IMMUNOLOGY
Volume 197, Issue 4, Pages 1308-1321Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1502481
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Funding
- NIAID NIH HHS [R01 AI113007, R01 AI049360, T32 AI007051, R56 AI049360, U19 AI109962] Funding Source: Medline
- NIAMS NIH HHS [P30 AR048311] Funding Source: Medline
- NIDDK NIH HHS [R01 DK084082] Funding Source: Medline
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T cells provide protective immunity against infections by differentiating into effector cells that contribute to rapid pathogen control and by forming memory populations that survive over time and confer long-term protection. Thus, understanding the factors that regulate the development of effective T cell responses is beneficial for the design of vaccines and immune-based therapies against infectious diseases. Cytokines play important roles in shaping T cell responses, and IL-10 has been shown to modulate the differentiation of CD4 and CD8 T cells. In this study, we report that IL-10 functions in a cell-extrinsic manner early following acute lymphocytic choriomeningitis virus infection to suppress the magnitude of effector Th1 responses as well as the generation of memory CD4 and CD8 T cells. We further demonstrate that the blockade of IL-10 signaling during the priming phase refines the functional quality of memory CD4 and CD8 T cells. This inhibition strategy resulted in a lower frequency of virus-specific follicular Th (Tfh) cells and increased the Th1 to Tfh ratio. Nevertheless, neither germinal center B cells nor lymphocytic choriomeningitis virus-specific Ab levels were influenced by the blockade. Thus, our studies show that IL-10 influences the balance between Th1 and Tfh cell differentiation and negatively regulates the development of functionally mature memory T cells.
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