Selective expansion of V gamma 2-V delta 7 TCR gamma delta cells in C57BL/6 mice is postnatal and extrathymic

Previous studies have shown that TCR- gamma delta cells expressing V gamma 2 region elements are selectively expanded in vivo in C57BL/6 (B6), but not DBA/2, mice. Genetic analysis demonstrated that the expansion of V gamma 2 super(+) was linked to the TCR alpha delta loci, suggesting that a particular V gamma -V delta pair may be necessary for the expansion. In the studies presented here, we find that the expanding TCR gamma delta cells in B6 mice express a V gamma 2 super(+)/V delta 7 super(+) TCR. The V gamma 2-J gamma and V delta 7-D delta -J delta 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 V gamma 2 super(+)/V delta 7 super(+) T cell expression were studied to determine the biological basis of clonal expansion. Although expression of the V gamma 2 super(+) cells in B6 and DBA/2 neonates was similar, V gamma 2 super(+) 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 V gamma 2 super(+) 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 V gamma 2 super(+) gamma delta T cells similar to their normally housed counterparts. Thus, expansion and diversification of V gamma 2 super(+) /V delta 7 super(+) T cells are postnatal extrathymic events that do not require microbial antigenic exposure.