TNF type 2 receptor (p75) lowers the threshold of T cell activation

EY Kim, HS Teh - The Journal of Immunology, 2001 - journals.aai.org
EY Kim, HS Teh
The Journal of Immunology, 2001journals.aai.org
T cell activation requires a threshold amount of TCR-mediated signals, an amount that is
reduced by signals mediated through costimulatory molecules expressed on the T cell
surface. Here the role of TNFR2 (p75) as a putative costimulatory receptor for T cell
activation was examined. It was found that p75 deficiency in CD8+ T cells increased the
requirements for TCR agonist approximately 5-fold. Furthermore, p75−/− T cells display a
marked reduction in the proliferative response to TCR agonist. This hypoproliferative …
Abstract
T cell activation requires a threshold amount of TCR-mediated signals, an amount that is reduced by signals mediated through costimulatory molecules expressed on the T cell surface. Here the role of TNFR2 (p75) as a putative costimulatory receptor for T cell activation was examined. It was found that p75 deficiency in CD8+ T cells increased the requirements for TCR agonist approximately 5-fold. Furthermore, p75−/− T cells display a marked reduction in the proliferative response to TCR agonist. This hypoproliferative response was associated with delayed kinetics of induction of the acute activation markers CD25 and CD69 as well as a marked decrease in the production of IL-2 and IFN-γ. The net result is that very few cells are recruited into the dividing population. Interestingly, CD28 costimulation was only partially effective in rescuing the proliferative defect of p75−/− CD8+ T cells. Thus, p75 provides an important costimulatory signal in addition to that provided by CD28 toward optimal T cell proliferation.
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