Spleen cells of dinitrophenyl keyhole limpet hemocyanin (DNPKLH) primed and boosted mice produced a nonantigen-specific helper factor upon in vitro challenge with DNPKLH. This helper factor displays all of the biological characteristics so far described for TRF produced by allogeneic or Concanavalin A stimulation of mouse spleen cells. It restores the primary anti-SRBC response in nude spleen cultures following the same kinetics of action as T-cell-replacing factor (TRF). Conversely, TRF restores the primary in vitro immune response of nude spleen cultures to DNPKLH. TRF also restores the secondary anti-hapten IgG response of T-cell-deprived spleen cell cultures derived from DNPKLH primed and boosted mice. Here the need for carrier specificity is fully overcome. The data therefore suggest that TRF, as a nonantigen-specific maturation signal, is involved in the primary and secondary immune responses to both particulate and soluble antigens.

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