Strain-specific TCR repertoire selection of IL-4-producing Thy-1dull γδ thymocytes

Abstract

Thy-1dull γδ thymocytes constitute an unusual subset of mature TCRγδ cells which share with NK T cells the expression of cell surface markers usually associated with activated or memory cells and the simultaneous production of high levels of IL-4 and IFN-γ upon activation. In DBA/2 mice, Thy-1dull γδ thymocytes express a restricted repertoire of TCR that are composed of the Vγ1 gene product mainly associated with Vδ6.4 chains exhibiting very limited junctional sequence diversity. In this study we have characterized this γδ T cell population in different strains of mice and show that Thy-1dull γδ thymocytes are present in every strain tested, albeit at different frequencies. Moreover IL-4 production by γδ thymocytes is mainly confined to the Thy-1dull γδ population in every strain tested. Finally, the repertoire of TCR expressed by Thy-1dull γδ thymocytes varies in different strain of mice, although a biased expression of Vγ1 and Vδ6 chains was observed in all strains studied. However, the extent of junctional diversity of the Vγ1 and Vδ6 chains expressed by Thy-1dull γδ thymocytes varied from oligoclonal in DBA/2 mice to polyclonal in FVB/N mice. Thy-1dull γδ thymocytes from mouse strains such as C3H/HeJ and BALB/c contain cells with diverse Vδ6(D)Jδ junctions together with cells with relatively homogeneous Vδ6(D)Jδ junctions, similar to those found in DBA/2. Thus, the Thy-1dull γδ population appears to contain two subsets of cells which differ in the diversity of their TCR.