Human thymocytes expressing gamma/delta T-cell receptors
Abstract
Expression of T-cell receptors of gamma/delta type characterizes a small subset of peripheral T lymphocytes which is homogeneously composed of cytolytic cells and, in most instances, lack CD4 and CD8 differentiation antigens. By the use of anti-TCR gamma/delta MAbs it is possible to identify two distinct subsets of TCR gamma/delta+ cells that are characterized by a Cγl or Cγ2-encoded forms of gamma-chain, respectively. While the BB3 MAb-reactive (Cγl encoded) cell subset is prevalent in peripheral blood (PB), these cells represent <10% in TCR gamma/delta+ thymocyte populations. In thymus, the majority of cells was found to react with delta-TCSI (or Al3) MAbs. Culture of CD4−8−thymocytes (highly enriched in TCR gamma/delta-cells) in IL-2 resulted in the de novo expression of CD8 surface antigen and of non MHC-restricted cytolytic activity. Cloning of CD4−8−thymocytes resulted, for the most part, in CD3+TCR gamma/delta- cells. Moreover, the majority of clones expressed the unusual delta-TCSI+ CD8+ phenotype and lysed the NK-sensitive K562 target cells. Analysis of the immunoprecipitated TCR molecules showed the existence of the (rare) heavy (55 kDa) form of gamma-chain. A redirected killing assay using murine P815 target cells and appropriate “stimulatory” antibodies was further employed for functional analysis of thymus-derived TCR gamma/delta+ clones. While anti-CD3 MAbs efficiently triggered the cytolytic activity of all clones irrespective of their phenotype, MAbs directed to TCR gamma/delta induced efficient lysis only of BB3+ or delta-TCSI+CD8− clones, but not of delta-TCSI+CD8+ clones. Therefore, it appears that a receptor type which appears to be relatively inefficient in mediating activation signals is predominant in the thymus and rare in the periphery.