TCR-GAMMA GENES ARE REARRANGED BUT NOT TRANSCRIBED IN IL-7R-ALPHA-DEFICIENT MICE

IL-7, a cytokine produced by bone marrow and thymic stroma, is a growt h factor for B and T lymphocytes very early in their development, The IL-7R is a heterodimer of an alpha-chain that specifically binds IL-7 and the common gamma-chain, gamma(c), which is also a component of the receptors for IL-2, IL-4, IL-9, and IL-15, IL-7 has also been hypothe sized to play a role in the differentiation of gamma delta T cells, wh ich is supported by the recent findings that mise deficient in the alp ha-chain of the IL-7R (IL-7R alpha-/-) or IL-7 (IL-7-/-) have a comple te absence of gamma delta T cells, but not alpha beta T cells, We shaw in this work that V gamma 4 and V gamma 6 TCR genes are rearranged, a nd sterile V gamma 4 and V gamma 6 TCR-gamma transcripts are expressed in IL-7R-/- -/- thymocytes, but these TCR-gamma genes, and V gamma 5, are not transcribed in thymocytes from IL-7R alpha-/- mice, RAG-1 and RAG-2 genes are transcriptionally active in fetal and adult IL-7R alp ha-/- thymocytes, The IL-7-inducible transcription factor, STAT5, is P lot active ia the fetal thymus of IL-7R alpha-/- compared with IL-7R a lpha+/+ mice. These data point to a specific role for IL-7/IL-7R signa ling in regulating the transcriptional activity, possibly mediated by SYAT5, of the rearranged TCR-gamma complex during development of gamma delta T cells, and point to mechanistic differences in the regulation of rearrangement of V gamma 4 and V gamma 6 genes vs V gamma 5.