Evidence For Controlled Gene Rearrangements and Cytokine Production During Development of Human TCRγδ+ Lymphocytes

Abstract

Molecular analysis of the TCRγ and δ loci has established that the number of V gene segments at these loci is limited. In man, nine functional Vγ gene segments have been described (Huck et al. 1988) and five Vδ gene segments (Takihara et al. 1989, Krangel et al. 1990). Potentially TCRγδ cells can use 54 different combinations of Vγ and δ gene segments. However, only a few combinations have been observed so far. Phenotypical analysis of TCRγδ+ T cell from peripheral blood has revealed that almost all of these cells use one of only two Vδ gene segments, Vδ1 and Vδ2. The majority of the TCRγδ+ T cells in most adults uses Vδ2 that pairs exclusively with Vγ2 (nomenclature of Strauss et al. 1987, Vγ2 = Vγ9 in the nomenclature of Huck et al. 1988). In contrast, in postnatal thymus TCRγδ+ T cells using Vδ1 predominate, whereas the Vδ2 using cells form a minority (Casorati et al. 1989). Parker et al. (1990) recently found that Vδ2+ cells undergo a postnatal extrathymic expansion which may explain why these cells constitute a majority of the TCRγδ+ T cell pool in most individuals. Those results, however, did not explain why there is a preferential pairing of γ and δ chains expressing Vγ2 and Vδ2. Transfection experiments have excluded that there is a physical constraint that prevents Vδ2 encoded δ chains to pair with other γ chains (Solomon et al. 1989). In this paper we discuss recent evidence that in man like in mouse, rearrangements at the γ and δ loci occur in a coordinated, ordered fashion during thymic development. This ordered rearrangements may partly explain why Vδ2 pairs predominantly with Vγ2. In addition, we discuss the findings that early fetal TCRγδ+ T cells and postnatal TCRγδ+ T cells produce different cytokines following activation.