Development of hapten-induced IL-4-producing CD4+ T lymphocytes requires early IL-4 production by αβ T lymphocytes carrying invariant Vα14 TCR α chains

This paper investigates the mechanisms responsible for the generation of IL-4-producing CD4(+) T cells during contact sensitization with the hapten trinitrochlorobenzene (TNCB). Lymph node cells taken 1 day after immunization spontaneously released IL-4 while lymph node cells taken 2 and 3 days after immunization did not produce IL-4, A second wave of IL-4 production that was both antigen-specific and MHC class II (I-A)-restricted was observed 4 days after immunization. The spontaneous release of IL-4 at day 1 was due to the alpha beta(+) double-negative (CD4(-)CD8(-)) T lymphocytes that also expressed NK1.1 and showed V(alpha)14 rearrangement, while alpha beta(+) CD4(+) T lymphocytes were the source of the antigen-specific IL-4 production at day 4. Early IL-4 production was required for the development of IL-4-producing CD4(+) T cells as mice injected with anti-V(alpha)14 or anti-IL-4 mAb produced little IL-4 and IL-10, while production of IFN-gamma was increased similar to 2-fold. These results indicate that the development of IL-4-producing CD4(+) T lymphocytes in the TNCB system requires early production of IL-4 by alpha beta(+) double-negative cells carrying invariant V(alpha)14 TCR alpha chain.