DEFINITION OF UNIQUE TRAITS OF HUMAN CD4-CD8-ALPHA-BETA-T-CELLS

We have studied the nature of human CD4-CD8- (double negative) alphabe ta T cells to determine whether they possess unique characteristics wh ich could further differentiate them from conventional CD4+ or CD8 + ( single positive) T cells. We observed that double negative TCR alphabe ta+ T cells differ from single positive T cells in the following respe cts: (i) their T cell receptor (TCR) repertoire is different, as revea led by the analysis of 47 clones derived from three individuals and by analysis of peripheral blood lymphocytes (PBL) prior to in vitro mani pulation; (ii) their in vivo CD3:TCR expression is lower before in vit ro manipulation and expansion; (iii) their direct proliferative respon se to IL-3, which is not mediated by secondary release of other T cell growth factors. These characteristics have also been recently ascribe d to murine double negative alphabeta T cells, which develop extrathym ically and are considered to be a distinct T cell lineage. Our data su ggest that, like their murine counterparts, human double negative alph abeta T cells may represent a distinct T cell lineage which might deve lop extrathymically.