HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Sathish, J. G. Articles by Matthews, R. J. Search for Related Content PubMed PubMed Citation Articles by Sathish, J. G. Articles by Matthews, R. J.

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 Function¹

Section of Infection and Immunity, Department of Medical Biochemistry and Immunology, School of Medicine, Cardiff University, Heath Park, Cardiff, United Kingdom

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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Project Grant 065556 from the Wellcome Trust and Project Grant G0100191 from the Medical Research Council (to R.J.M.) and a PhD Studentship from the Tenovus Charity (to G.D.).

² Current address: Division of Pharmacology and Therapeutics, School of Biomedical Sciences, Sherrington Buildings, University of Liverpool, Liverpool, U.K.

³ Address correspondence and reprint requests to Dr. R. James Matthews, Section of Infection and Immunity, Department of Medical Biochemistry and Immunology, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XX, U.K.

⁴ Abbreviations used in this paper: DC, dendritic cell; LN, lymph node; SHP-1, Src homology region 2 domain-containing protein tyrosine phosphatase.