Selective deficiency in IL-2 production and refractoriness to extrinsic IL-2 in immunodeficiency with hyper-IgM

Various lymphokines are inducible by the stimulation of T-cell mitogens, phytohemagglutinin, and concanavalin A. A 32-year-old female with an atypical type of immunodeficiency with hyper-IgM was evaluated for possible defects in the production of several immunoregulatory lymphokines. Although the mitogens appeared to bind effectively to the specific surface receptors of patient peripheral blood lymphocyte (PBL), the proliferative responses were significantly decreased. The culture supernatant of patient PBL stimulated by the mitogens contained only a trace amount of interleukin 2 (IL-2) activity. Addition of recombinant IL-2 to the cultures concomitantly with the mitogens could not restore the decreased responses of patient PBL. Tac antigen expression of patient PBL induced by the mitogens was moderately impaired. These data suggest that there is a defect in both IL-2-producing and IL-2-responding cells. In contrast, the culture supernatant of mitogen-stimulated patient PBL contained B-cell growth and differentiation factors as well as interferon-gamma activities equal to those of the control. These results suggest that there are independent regulatory pathways for the production of IL-2 and other T-cell-derived lymphokines.