PHENOTYPIC AND FUNCTIONAL MATURATION OF TCR GAMMA-DELTA CELLS IN THE HUMAN THYMUS

In contrast to thymic differentiation of TCR alpha beta cells, differe ntiation stages of TCR gamma delta cells are largely unknown, This rep ort shows that CD1, a known marker of immature TCR alpha beta thymocyt es, was expressed on some postnatal TCR gamma delta thymocytes. Only C D1(+) TCR gamma delta thymocytes expressed recombination-activating ge ne-1 mRNA, and they were shown to differentiate into CD1(-) TCR gamma delta thymocytes. Functionally, sorted CD1(-) TCR gamma delta thymocyt es proliferated in the presence of immobilized anti-CD3 Ab plus exogen ous rIL-2 or rIL-15. Interestingly, in contrast to CD1(-) TCR gamma de lta cells, CD1(-) TCR gamma delta thymocytes also proliferated extensi vely when cultured with exogenous rIL-2 or rIL-15 alone, FAGS analysis as well as reverse transcription-PCR analysis showed that only CD1(-) TCR gamma delta thymocytes expressed IL-2R beta protein and mRNA, The differential expression of maturation markers, such as CD27, CD45RO, and CD45RA, as a function of expression of CD1 was similar in TCR gamm a delta and TCR alpha beta thymocytes. An important exception is the e xpression of CD4 and CD8. Whereas TCR alpha beta thymocytes are mainly CD4-CD8 double positive at the immature CD1(+) stage and CD4 or CD8 s ingle positive at the mature CD1(-) stage, CD1(bright) TCR gamma delta thymocytes all expressed CD4, but only some of them expressed CD8, So me CD1(-) TCR gamma delta thymocytes also expressed CD8, but were nega tive for CD4. Collectively, our data clearly show that CD1 is a useful marker to distinguish immature human TCR gamma delta thymocytes from functional mature gamma delta cells based on recombination-activating gene-1 expression, in vitro differentiation, and phenotypic and functi onal characteristics.