The role of programmed death-1 (PD-1) expression in the negative selection of T lymphocytes
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Abstract
The immune system must be able to mount a response against pathogens and transformed cells while remaining tolerant to healthy host tissue. A key process for ensuring this self-tolerance is the negative selection of self-reactive thymocytes. Expression of Programmed Death-1 (PD-1), a co-inhibitory member of the CD28 family associated with dampened peripheral immune responses,was found to be upregulated in 20-40% of thymocytes undergoing negative selection in the HYcd4model of thymic development. Although analysis of gene and protein expression directly ex vivo indicates that PD-1- and PD-1+ thymocytes are equally apoptotic, PD-1+ thymocytes appear to be protected from apoptosis in an in vitro stimulation assay. Analysis of HYcd4PD-1-/- mice indicates that thymocytes receive a higher intensity signal in the absence of PD-1. Future work utilizing HYcd4PD-1-/- mice will increase our understanding of the role of PD-1 in thymic negative selection.