Thymus-dependent and thymus-independent developmental pathways for peripheral T cell receptor-γδ-bearing lymphocytes

To elucidate the developmental pathways of T cells that bear TCR-γδ, we have analyzed the kinetics of expression and biochemical characteristics of γδ receptors in the thymus and spleen of normal and athymic (nude) mice, as well as nude mice engrafted with neonatal thymuses. TCRγδ-bearing thymocytes and splenocytes have a CD4^-8^- phenotype, and both populations express products of the Cγ1 locus. TCRγδ-bearing cells develop in the thymus before their appearance in the spleen. Young nude mice have no detectable TCRγδ-bearing cells in their spleens. When young nude mice are given thymus grafts, TCRγδ-bearing cells of host origin first develop in the engrafted thymus, followed by their appearance in the spleen. In the absence of a thymus graft, the spleens of old nude mice eventually develop small numbers of TCRγδ⁺ cells, as well as TCRαβ⁺ cells. These results demonstrate that there is a major thymic-dependent pathway for TCRγδ expression, as well as a minor thymic-independent pathway seen in older nude mice. The development of TCRγδ⁺ cells in the thymus before their appearance in the spleen, both in normal ontogeny as well as in the thymus-engrafted nude mouse model, suggests that thymic TCRγδ⁺ cells are precursors of the thymus-dependent population of peripheral TCRγδ⁺ cells.