Interferon-gamma restores T lymphocyte proliferation of nonresponders to IgG1 anti-CD3 via the induction of Fc gamma 1 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 IgG1 (or IgG2a) antibodies is due to a failure of their monocytes to bind these IgG isotypes. In this study, we have selected such nonresponder subjects to IgG1 anti-CD3 (UCHT 1) in order to study their monocytes. Two assays were used: IgG1 and IgG2 EA 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 IgG1 anti-CD3 monocyte chemiluminescence strictly correlates with the absence of IgG1 EA rosettes. Thus, the failure to respond to UCHT 1, in all nonresponders tested to date, is due to the absence of Fc gamma 1 receptors on their monocytes. Treatment of nonresponder monocytes by recombinant interferon-gamma was shown to restore T cell proliferation and monocyte chemiluminescence in nonresponders. This effect of interferon-gamma correlates with the appearance of Fc gamma 1 receptors on monocytes from these individuals. This work strongly suggests that nonresponder monocytes possess functional genes for Fc gamma 1 receptors which are not expressed normally at a detectable level but can be induced by interferon-gamma.
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface / Q000276:immunology*; D002478:Cells, Cultured; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000494:pharmacology*; D008163:Luminescent Measurements; D008213:Lymphocyte Activation; D009000:Monocytes / Q000276:immunology*; D011961:Receptors, Fc / Q000276:immunology*; D017452:Receptors, IgG; D012397:Rosette Formation; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D007074:Immunoglobulin G; D011961:Receptors, Fc; D017452:Receptors, IgG; D007371:Interferon-gamma