INTERLEUKIN-7 INDUCES TCR GENE REARRANGEMENT IN ADULT MARROW-RESIDENTMURINE PRECURSOR T-CELLS

Rearrangement of the T cell antigen receptor genes is a complex, highl y regulated process. To gain a better understanding of the extracelluI ar factors involved in the regulation of TCR beta and gamma gene rearr angement in adult murine bone marrow-resident precursor T cells, sever al cytokines were tested for their ability to induce gene recombinatio n. A selected population of C58/J bone marrow cells (Thy 1(low), CD3(- ), CD8(-), B220(-)) that is enriched for pre-T cell activity was propa gated in vitro in medium supplemented with IL-3 and mast cell growth f actor (MGF, also referred to as stem cell factor, Steele factor and c- kit ligand). These cytokines were required for the maintenance of pre- T cell activity in culture, but had no effect on TCR gene expression. Several additional cytokines were added to the culture medium. Of all those tested, only IL-7 induced complete rearrangement of the TCR gamm a locus. Complete rearrangement of the TCR beta locus was not induced under any of the culture conditions analysed here. The bone marrow cel ls cultured in IL-3, MGF and IL-7 did not begin to express mature T ce ll proteins and maintained their in vivo progenitor potential. Further more, IL-7 cultured bone marrow cells were capable of differentiation in vivo into all phenotypic subpopulations of T cells, without an appa rent bias toward the gamma delta lineage. The data presented here sugg est that TCR gamma gene rearrangement in adult pre-T cells is regulate d by IL-7, but that the TCR beta locus requires additional or alternat ive signals for the induction of complete rearrangement. (C) 1997 Else vier Science Ltd.