IMMUNE TOLERANCE AND PROTECTION AGAINST ALLERGIC SENSITIZATION

Recent studies in our laboratory have focused on the nature of the pri mary T-cell response to inhaled allergens in the regional lymph nodes (RLN) draining the upper airways, in immunologically naive mice and ra ts. In general terms, the first detectable response involves activatio n of allergen-specific interleukin 4 (IL-4) secreting CD4(+) Th-0/Th-2 cells, which triggers (at least in genetically high-immunoglobulin E (IgE)-responders) an initial burst of IgE antibody synthesis. This is followed by a rapidly expanding interferon gamma (IFN-gamma) response in the RLN, which terminates IL-4 secretion and IgE production. We hav e presented evidence that the initial source of IFN-gamma in this resp onse is a population of major histocompatibility complex (MHC) class I restricted CD8(+) T-cells, which respond specifically to the allergen . The initial activation of these CD8(+) T-cells requires a source of exogenous IL-2, which appears to be supplied by the Th-0/Th-2 cells, w hich are themselves eventually suppressed by the cytokine products of the CD8(+) T-cells. It is hypothesized that the IFN-gamma-rich milieu created by the allergen-specific CD8(+) T-cells eventually selects for allergen-specific Th-1 cells, which, with chronic stimulation, eventu ally outgrow the CD8(+) population and become dominant in the allergen -specific T-cell memory pool. Our most recent experiments have identif ied a previously covert but highly potent effector cell subset within the CD8(+) T-cell population, in the form of allergen-specific TcR1 (g amma/delta) T-cells. Less than 500 of these cells, purified by positiv e sorting, are required to regulate the CD4 T-cell response in adult m ice or rats, in adoptive transfer experiments. This suggests that thes e CD8(+) T gamma/delta cells exert their function via a powerful ampli fication loop that involves the rapid recruitment of other ''Th-2 inhi bitory'' effector cells during the initial stages of the immune respon se.