Infection of Adult Thymus with Murine Retrovirus Induces Virus-Specific Central Tolerance That Prevents Functional Memory CD8 T Cell Differentiation

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During thymocyte development, cells that recognize self-antigens are specifically deleted by the process known as negative selection. However, some pathogens disseminate to the thymus, and can induce foreign antigen presentation within this organ, resulting in potentially harmful clonal deletion of pathogen-specific T-lymphocyte precursors. In chronic infections, pathogen-specific T cells in the periphery progressively lose their functionality due to continual stimulation with the persisting antigen, a phenomenon known as T cell exhaustion. However, pathogen-reactive naïve T cells freshly primed during the chronic phase of infection can nevertheless replenish the functional pool of memory T cells. Therefore, a lack of their generation in the face of peripheral exhaustion may ultimately cause the loss of functional memory T cells and the resultant lack of pathogen control. In this study, we demonstrate that Friend murine retrovirus can utilize the above immune evasion strategy, a combination of ongoing peripheral exhaustion and virus-induced central tolerance. Our data suggest that, along with the reinvigoration of exhausted T cells in the periphery, preservation of the thymic function in supplying pathogen-specific naïve T cells may be important when considering immunological control of chronic infection with thymotropic pathogens.

Vyšlo v časopise: Infection of Adult Thymus with Murine Retrovirus Induces Virus-Specific Central Tolerance That Prevents Functional Memory CD8 T Cell Differentiation. PLoS Pathog 10(3): e32767. doi:10.1371/journal.ppat.1003937
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1003937

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