Immune tolerance and protection against allergic sensitization.
Recent studies in our laboratory have focused on the nature of the primary T-cell response to inhaled allergens in the regional lymph nodes (RLN) draining the upper airways, in immunologically naive mice and rats. In general terms, the first detectable response involves activation 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 have presented evidence that the initial source of IFN-gamma in this response 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, which 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, eventually outgrow the CD8+ population and become dominant in the allergen-specific T-cell memory pool. Our most recent experiments have identified a previously covert but highly potent effector cell subset within the CD8+ T-cell population, in the form of allergen-specific TcR1 (gamma/delta) T-cells. Less than 500 of these cells, purified by positive sorting, are required to regulate the CD4 T-cell response in adult mice or rats, in adoptive transfer experiments.(ABSTRACT TRUNCATED AT 250 WORDS)
Holt
P G
PG
Division of Cell Biology, Institute for Child Health Research, West Perth, Western Australia.
D000485:Allergens / Q000276:immunology; D000818:Animals; D000917:Antibody Formation; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000517:prevention & control*; D007107:Immune System / Q000502:physiology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000502:physiology; D012119:Respiration
D000485:Allergens; D016692:Receptors, Antigen, T-Cell, gamma-delta