Regulation of T cell homeostasis by the transmembrane adaptor protein SIT.
The transmembrane adaptor protein SIT is a negative regulator of TCR-mediated signaling. However, little is known about the functional role of SIT in mature T cells. In this study, we show that mice deficient for SIT display a decreased number of naive CD8(+) T cells and a progressive accumulation of memory-like (CD44(high)) CD8(+) T lymphocytes that resemble cells undergoing homeostatic proliferation. Indeed, when transferred into lymphopenic hosts, SIT(-/-) naive CD8(+) T cells undergo enhanced homeostatic proliferation and express a higher level of CD44 in comparison to wild-type T cells. By using class-I-restricted TCR transgenic models with different ligand affinity/avidity, we show that lymphopenia-induced homeostatic proliferation is more pronounced in cells carrying low-affinity TCRs. Strikingly, the loss of SIT induces homeostatic proliferation of HY TCR transgenic cells, which are normally unable to proliferate in lymphopenic mice. Collectively, these data demonstrate that SIT negatively regulates T cell homeostasis. Finally, we show that SIT-deficient T cells develop a mechanism analogous to sensory adaptation as they up-regulate CD5, down-regulate the coreceptor, and display impaired TCR-mediated ZAP-70 activation.
Posevitz
Vilmos
V
Institute of Molecular and Clinical Immunology, Otto-von-Guericke University, Leipziger Strasse 44, Magdeburg, Germany.
Arndt
Boerge
B
Krieger
Tina
T
Warnecke
Nicole
N
Schraven
Burkhart
B
Simeoni
Luca
L
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000502:physiology*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D006706:Homeostasis / Q000235:genetics; D018960:Hyaluronan Receptors / Q000032:analysis; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D015398:Signal Transduction
D048868:Adaptor Proteins, Signal Transducing; D018960:Hyaluronan Receptors; D008565:Membrane Proteins; C503874:SIT protein, mouse