Selective expansion of Vgamma2-Vdelta7 TCR gammadelta cells in C57BL/6 mice is postnatal and extrathymic.

Abstract

Previous studies have shown that TCR-gammadelta cells expressing Vgamma2 region elements are selectively expanded in vivo in C57BL/6 (B6), but not DBA/2, mice. Genetic analysis demonstrated that the expansion of Vgamma2+ was linked to the TCR alphadelta loci, suggesting that a particular Vgamma-Vdelta pair may be necessary for the expansion. In the studies presented here, we find that the expanding TCR gammadelta cells in B6 mice express a Vgamma2+/Vdelta7+ TCR. The Vgamma2-Jgamma and Vdelta7-Ddelta-Jdelta junctional amino acid sequences of these cells display wide variation in length, suggesting that expansion is based on variable region usage and not junctional diversity. The kinetics and dynamics of Vgamma2+/Vdelta7+ T cell expression were studied to determine the biological basis of clonal expansion. Although expression of the Vgamma2+ cells in B6 and DBA/2 neonates was similar, Vgamma2+ cells in the B6 mice expanded fourfold by 4 wk of age, while the expression in DBA/2 mice remained constant. In addition, expansion of the Vgamma2+ cells occurred in athymic nude mice, suggesting that expansion was driven by extrathymic stimuli. Finally, B6 mice housed under germfree conditions expressed expanded levels of Vgamma2+ gammadelta T cells similar to their normally housed counterparts. Thus, expansion and diversification of Vgamma2+/Vdelta7+ T cells are postnatal extrathymic events that do not require microbial antigenic exposure.