Specific immune response enhancing factor in serum of immunised mice

Abstract

ONE of the central problems of immunology is the mechanism by which regulatory thymus derived T cells—T helper, T amplifier and T suppressor cells—interact with each other and with the precursor cells of the antibody-forming B lymphocytes. Various mediators produced by T cells acting directly or indirectly on B cells have been described. Some of these factors have been shown to enhance^1–4 or to suppress^5,6 the function of B cells either in an antigen-specific^1,2,5 or in a nonspecific^3,4,6 manner. Immune response-enhancing factors produced in vitro have been shown to replace T helper or T amplifier cell function in thymus-dependent antibody formation in vivo^1,2 and/or in vitro^1–4. We show here that the serum (S₄) of mice injected 4 h previously with a super-optimal dose of sheep red blood cells (SRBC) contains an antigen-specific principle—specific immune response enhancing factor (SIREF)—which enhances the humoral immune response up to 60-fold when injected before a sub-optimal antigen dose into mice but not in mice injected with an optimal dose of antigen (2×10⁸ SRBC). SIREF could not be produced in athymic nude mice and SIREF produced in BALB/c (H₂d) or C57B1 (H₂b) mice acted in either strain, but not in athymic mice (Table 1). These results indicate that SIREF(1) may be released from T cells (or from B cells which require T-cell cooperation), (2) acts through the H₂ barrier, and (3) does not act directly on B cells.