Identification of lacrimal gland associated immunomodulatory activities having differential effects on T and B cell proliferative responses.

The supernatants from overnight cultures of rat lacrimal glands (LGSN) were found to suppress the proliferative response of rat splenic mononuclear cells following mitogenic stimulation. LGSN inhibited LPS and STM responses to a greater degree (55% inhibition at 1.56% v/v) than ConA and PHA responses (9 and 28% inhibition, respectively, at 1.56% v/v). PWM-induced responses were inhibited at an intermediate level (32% inhibition at 1.56% v/v). The inhibitory activity was not mediated by a suppression of lymphokine production, as the activity was not reversed by the addition of exogenous recombinant IL-2 (25 U/ml) or conditioned medium from allogeneic mixed lymphocyte reactions, nor was the suppressive activity mediated by a nonspecific cytotoxic effect. Dialysis of LGSN indicated that species less than 3500 Da were able to inhibit all mitogenic responses whereas factors greater than 3500 Da were only able to inhibit LPS and STM responses. LGSN were shown to contain prostaglandin E2, however, at levels which were insufficient to explain the low molecular weight inhibitory activity. In addition to the inhibition of mitogenic responses, LGSN also inhibited B cell hybridoma and growth factor (IL-2, IL-4) dependent T cell proliferation, an inhibition which was abrogated following dialysis. These findings suggest the presence of multiple factors in rat lacrimal glands which are able to modulate T and B cell proliferative responses.