INCREASED INTERLEUKIN-4 AND IMMUNOGLOBULIN-E PRODUCTION IN TRANSGENICMICE OVEREXPRESSING NK1T CELLS

Natural Killer (NK)1.1(+) (NK1) T cells are a specialized subset of al pha/beta T cells that coexpress surface receptors that are normally as sociated with the NK cell lineage of the innate immune system. On reco gnition of the conserved, major histocompatibility complex class I-lik e CD1 molecule, these cells are able to release explosive bursts or in terleukin 4 (IL-l), a cytokine that promotes the T helper type 2 (Th2) effector class of an immune response, A unique feature of their T cel l receptor (TCR) repertoire is the expression of an invariant TCR alph a chain, V alpha 14-J alpha 281, and of a restricted but polyclonal se t of V beta gene families, V beta 8, V beta 7, and V beta 2. Here, we show that transgenic expression of this TCR a chain during thymic deve lopment is sufficient information to bias the differentiation of mains tream thymocytes towards the NK1 developmental pathway. It markedly in creases the frequency of cells with the NK1 pattern of T cell differen tiation and also has drastic consequences for the selection of the V b eta repertoire. Transgenic CD4 cells exhibited a 10-100-fold increase in IL-4 production on mitogen stimulation in vitro and in vivo, and ba seline levels of the Th2-controlled serum immunoglobulin isotypes, IgE and IgG1, were also selectively elevated in vivo.