Specific IgG autoantibodies are potent inhibitors of autoreactive T cell response to phytohemagglutinin-activated T cells.

PHA-activated human T cells express MHC class II molecules and have been shown to stimulate autoreactive T cells in autologous mixed lymphocyte reaction (T-T AMLR). We now demonstrate that normal human serum can dramatically suppress the proliferative response in T-T AMLR. The inhibitory factor was detected in the IgG fraction, and the activity was found to be mediated through the F(ab')2 portion of the IgG molecule, implying that the inhibitor could be specific. All homologous as well as autologous sera tested contained the inhibitory activity. Human serum was also found to suppress allogenic MLR stimulated by PHA-activated T lymphocytes but not allogenic MLR stimulated by nonactivated PBMC, indicating that the mechanism of inhibition is related to PHA activation of the stimulator cells. Moreover, pretreatment of the PHA-activated T lymphocytes with human serum resulted in a significant inhibition of T-T AMLR, as opposed to pretreatment of nonactivated PBMC, indicating that PHA-activated stimulators are functionally involved in the inhibition. Cytofluorometric analysis revealed that autologous IgG specifically binds to PHA-activated T lymphocytes and not to nonactivated CD3+ T cells. Furthermore, serum absorbed by PHA-activated T lymphocytes substantially lost its inhibitory activity whereas serum absorbed by nonactivated PBMC did not, suggesting that a surface molecule(s) expressed during activation of the stimulator cells is involved in the inhibition. The addition of human serum later in the culture period (> 3 days) resulted in a marked decrease in inhibition, implying that the presence of IgG in the early recognition phase of T-T AMLR is essential for maximum inhibitory effect. These results raise the possibility that natural autoantibodies present in normal human IgG may play an important role in regulating immune response mediated by autoreactive T cells.