| First Author | Sathish JG | Year | 2007 |
| Journal | J Immunol | Volume | 178 |
| Issue | 1 | Pages | 330-7 |
| PubMed ID | 17182570 | Mgi Jnum | J:141929 |
| Mgi Id | MGI:3820035 | Doi | 10.4049/jimmunol.178.1.330 |
| Citation | Sathish JG, et al. (2007) Loss of Src homology region 2 domain-containing protein tyrosine phosphatase-1 increases CD8+ T cell-APC conjugate formation and is associated with enhanced in vivo CTL function. J Immunol 178(1):330-7 |
| abstractText | Extensive evidence has been accumulated to implicate the intracellular protein tyrosine phosphatase, Src homology region 2 domain-containing protein tyrosine phosphatase-1 (SHP-1), as a negative regulator of TCR-signaling thresholds. Specifically, T cells from the SHP-1-deficient mouse, motheaten, exhibit a hyperproliferative phenotype when activated by cognate peptide-pulsed APCs. However, the cellular basis for this phenotype has not been fully explained. Using the intracellular fluorescent dye, CFSE, we show that a greater proportion of motheaten vs control naive CD8(+) T cells undergo cell division when activated by peptide-pulsed APCs. Furthermore, there is a greater likelihood of TCRs on SHP-1-deficient vs control T cells binding to peptide/MHC ligands on APCs when using TCR down-regulation as an indirect measure of TCR engagement. In addition, T cell-APC conjugate assays provide direct evidence that a greater proportion of SHP-1-deficient T cells are capable of forming stable conjugates with APCs and this may explain, at least in part, their hyperproliferative response to TCR-triggered stimulation. The physiological relevance of the combined in vitro observations is demonstrated by the significantly enhanced in vivo expansion and CTL capacity generated in mice receiving adoptively transferred SHP-1-deficient naive CD8(+) T cells when compared with control T cells. |
