INTERLEUKIN-1 FAVORS THE IN-VITRO DEVELOPMENT OF TYPE-2 T-HELPER (TH2) HUMAN T-CELL CLONES

The effects exerted by interleukin-l (IL1) on the growth and differentiation of human Th1 and Th2 cells were examined. Neither IL1 nor the IL1 receptor antagonist (IL1ra) had detectable activity toward the antigen- or anti-CD3 antibody-induced proliferative response of already established type 1 T helper (Th1) or type 2 T helper (Th2) clones. Moreover, neither exogenous IL1 addiction to, nor neutralization of, endogenously produced Ill in bulk cultures before cloning changed the Th1-like cytokine profile of PPD-specific T-cell lines. Likewise, IL1 addition in bulk culture before cloning did not significantly affect the Th2-like cytokine profile of Der.p.I-specific T-cell lines (Dermatophagoides pteronyssinus group I). However, Der.p.I-specific T-cell lines, derived in the presence of anti-ill Ab, IL1ra or the M-20 IL1 inhibitor, exhibited the reduced ability to produce IL4 and an increased ability to produce interferon gamma (IFN I). More importantly, Der.p.I-specific T-cell lines derived in the presence of IL1ra developed into Der.p.I-specific CD4(+) T-cell clones showing a Th0/Th1-like, instead of a Th0/Th2-like, cytokine profile. These data suggest that IL1 is not required for the growth of already established human Th1 or Th2 CD4(+) T-cell clones and has no regulatory effects on the in vitro development of Th1-like cells, but it plays a critical role in the development of Th2-like cells.