Abstract
CD4+ T cells differentiate in the thymus from committed precursors to mature naive cells ready for peripheral circulation. Successful maturation depends on adequate but not excessive signaling upon T cell receptor (TCR) engagement of selfpeptide/MHC class II molecule ligands present in the thymic environment. Persistent TCR signaling throughout development from the CD4+CD8+ to the CD4+ state is required for completion of the developmental process. Recent work has suggested that a continuation of this signaling is essential for sustained survival of CD4+ T cells once they leave the thymus but our studies suggest otherwise. Although we found clear evidence for active TCR signaling involving recognition of self-ligands in peripheral lymphoid tissues, we did not see a substantial effect of loss of such signaling on the life-time of naive CD4+ T cells. Based on a careful review of the literature, we conclude that essentially all previous claims that MHC class II recognition plays a significant role in the survival of CD4+ T cells can be reinterpreted as an effect of self-recognition on proliferation in lymphopenic environments, maintaining population numbers without a marked effect on individual cell viability. We propose a possible explanation for why, in contrast, the viability of naive CD8+ T cells appears to show such self-MHC dependence and suggest that a primary function of self-recognition by T cells may be to enhance responses to foreign antigen.
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Germain, R.N., Stefanova, I., Dorfman, J. (2002). Self-Recognition and the Regulation of Cd4+ T Cell Survival. In: Gupta, S., Butcher, E., Paul, W. (eds) Lymphocyte Activation and Immune Regulation IX. Advances in Experimental Medicine and Biology, vol 512. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0757-4_13
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DOI: https://doi.org/10.1007/978-1-4615-0757-4_13
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