Regulating naïve and memory CD8 T cell homeostasis--a role for protein tyrosine phosphatases

A complex network of signalling events coordinate the differentiation, activation and maintenance of T lymphocytes. Tyrosine phosphorylation and dephosphorylation by protein tyrosine kinases and protein tyrosine phosphatases (PTPs) respectively, are critical for the activation and propagation of these signalling cascades. Intriguingly, the removal of tyrosyl phosphate moieties from phosphorylated proteins by phosphatases can contribute to both the positive and negative regulation of signalling events. The complex and diverse roles of individual PTP family members in immune cells is evident by the range of immune disorders caused by PTP deficiencies. Central to several such immune disorders is the disturbance of T cell homeostasis, as characterized by aberrant cell growth, survival and activation. The survival and homeostatic proliferation of naïve and memory CD8 T cells is primarily regulated by signalling events downstream of the T cell receptor complex and common γ chain cytokine receptors, events frequently targeted by PTP activity. We review the primary PTPs involved in CD8 T cell homeostasis, focusing on the signalling nodes that they target. In addition, because the mechanisms that co-ordinate PTP activity are only partially understood, we discuss currently proposed models of regulation and highlight unanswered questions.