DEVELOPMENT OF HAPTEN-INDUCED IL-4-PRODUCING CD4(-LYMPHOCYTES REQUIRES EARLY IL-4 PRODUCTION BY ALPHA-BETA T-LYMPHOCYTES CARRYING INVARIANTV(ALPHA)14 TCR ALPHA-CHAINS() T)

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 aft er immunization spontaneously released IL-4 while lymph node cells tak en 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(a lpha)14 rearrangement, while alpha beta(+) CD4(+) T lymphocytes were t he 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 produce d little IL-4 and IL-10, while production of IFN-gamma was increased s imilar to 2-fold. These results indicate that the development of IL-4- producing CD4(+) T lymphocytes in the TNCB system requires early produ ction of IL-4 by alpha beta(+) double-negative cells carrying invarian t V(alpha)14 TCR alpha chain.