Production of interleukin-4 and interferon-gamma by TCR-V beta-expressing T-cell subsets in allergen-sensitized mice.

Abstract

Sensitization of BALB/c mice to ovalbumin (OVA) through the airways stimulated allergen-specific immediate hypersensitivity responses and these effects were related to the expansion of V beta 8.1/8.2+ T cells. In contrast, splenic V beta 2+ T cells from sensitized animals inhibited V beta 8.1/8.2+ T-cell induction of anti-OVA IgE production in vivo. To examine whether such differences in T-cell function were associated with differences in cytokine production, CD4+ T cells and CD4+ T cells depleted of V beta 8.1/8.2+ T cells were analyzed for interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) production. In nonsensitized animals, no differences in IL-4 and IFN-gamma production were found in mRNA levels as well as in protein levels in these two populations of cells. In contrast, CD4+ T cells from sensitized mice showed higher IL-4 and lower IFN-gamma production than CD4+ cells depleted of V beta 8+ lymphocytes. Similar results were obtained after stimulation of CD4+ T cells from OVA-sensitized animals with anti-V beta 2 and anti-V beta 8.1/8.2 antibodies. Stimulation of V beta 8.1/8.2+ T cells from sensitized mice with OVA or OVA peptide 323-339 also resulted in increased production of IL-4. These data indicate that allergen sensitization via the airways stimulates the selective expansion of certain V beta-expressing T cells and that these T-cell subsets exhibit different functional activities in terms of cytokine production.