Polyfunctional T cells — having the ability to secrete cytokines and chemokines and to mediate cytolysis — are highly predictive of protective immunity but often become exhausted in chronic infections in response to persistent antigen stimulation, through a mechanism that is only partly determined by the upregulation of inhibitory receptors such as programmed cell death protein 1 (PD1). This study shows that high antigen concentration decreases the proportion of polyfunctional T cells in both memory and naive CD8+ T cell populations in a manner independent of PD1 signalling but dependent on the MAPK ERK pathway. High levels of antigen upregulate expression of sprouty 2 (SPRY2), a negative regulator of MAPK ERK signalling. HIV-specific patient T cells have increased levels of SPRY2, and SPRY2 knockdown in these T cells increased HIV-specific polyfunctionality.
References
Chiu, Y.-L. et al. Sprouty-2 regulates HIV-specific T cell polyfunctionality. J. Clin. Invest. http://dx.doi.org/10.1172/JCI70510 (2013)
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Minton, K. Mechanisms of T cell polyfunctionality. Nat Rev Immunol 14, 7 (2014). https://doi.org/10.1038/nri3596
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DOI: https://doi.org/10.1038/nri3596