Cutting edge: inhibition of T cell activation by TIM-2.
T cell Ig and mucin domain protein 2 (TIM-2) has been shown to regulate T cell activation in vitro and T cell-mediated disease in vivo. However, it is still not clear whether TIM-2 acts mainly to augment T cell function or to inhibit it. We have directly examined the function of TIM-2 in murine and human T cell lines. Our results indicate that expression of TIM-2 significantly impairs the induction of NFAT and AP-1 transcriptional reporters by not only TCR ligation but also by the pharmacological stimuli PMA and ionomycin. This does not appear to be due to a general effect on cell viability, and the block in NFAT activation can be bypassed by expression of activated alleles of Ras or calcineurin, or MEK kinase, in the case of AP-1. Thus, our data are consistent with a model whereby TIM-2 inhibits T cell activation.
Knickelbein
Jared E
JE
Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
de Souza
Anjali J
AJ
Tosti
Richard
R
Narayan
Preeti
P
Kane
Lawrence P
LP
D000818:Animals; D019703:Calcineurin; D002460:Cell Line; D006801:Humans; D008213:Lymphocyte Activation; D020930:MAP Kinase Kinase Kinases; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D050778:NFATC Transcription Factors / Q000037:antagonists & inhibitors; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013601:T-Lymphocytes / Q000502:physiology*; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors; D018631:ras Proteins
D008565:Membrane Proteins; D050778:NFATC Transcription Factors; D011948:Receptors, Antigen, T-Cell; C442242:Timd2 protein, mouse; D018808:Transcription Factor AP-1; D020930:MAP Kinase Kinase Kinases; D019703:Calcineurin; D018631:ras Proteins