Interferon-y restores T lymphocyte proliferation of nonresponders to IgGl anti-CD3 via the induction of Feyl receptors on monocytes*
Human peripheral blood T lymphocytes are stimulated to grow and divide by some mouse anti-CD3 monoclonal antibodies. This polyclonal mitogenesis is dependent on both their immunoglobulin subclass and the presence of monocytes. The unresponsiveness of T lymphocytes from certain individuals to mouse IgGl (or IgG2,) antibodies is due to a failure of their monocytes to bind these IgG isotypes. In this study, we have selected such nonresponder subjects to IgGl anti-CD3 (UCHT 1) in order to study their monocytes. Two assays were used: IgGl and IgG2 E A rosettes to evaluate their Fc receptor-binding capacity, and IgG-mediated monocyte chemiluminescence to test their receptor-related activation since mouse anti-T cell antibodies binding to lymphocytes trigger monocyte chemiluminescence via their Fc receptor. We have observed that in all nonresponder subjects the absence of IgGl anti-CD3 monocyte chemiluminescence strictly correlates with the absence of IgGl E A rosettes. Thus, the failure to respond to UCHT1, in all nonresponders tested to date, is due to the absence of Fcyl receptors on their monocytes. Treatment of nonresponder monocytes by recombinant interferon-y was shown to restore T cell proliferation and monocyte chemiluminescence in nonresponders. This effect of interferon-y correlates with the appearance of Fcyl receptors on monocytes from these individuals. This work strongly suggests that nonresponder monocytes possess functional genes for Fcyl receptors which are not expressed normally at a detectable level but can be induced by interferon-y.