Cellular regulation of gamma interferon production: Lyt phenotype of the suppressor cell.

Abstract

Suppressor cell activity for in vitro gamma interferon (IFNgamma) production can be induced in C57BL/6 mice with the T-cell mitogens staphylococcal enterotoxin A and concanavalin A. The suppressor cell lacked mitogen specificity in that injection of mice with either staphylococcal enterotoxin A or concanavalin A induced potent suppressor cell activity that inhibited the in vitro induction of IFNgamma by either mitogen. The suppressor cell is a T cell with a relatively high density of Thy 1 antigen. The IFNgamma-producing cell has a low density of Thy 1 and appears to have evolved from cells with a high density of Thy 1.2 or to have required such cells as helpers in the production of IFNgamma. Monoclonal anti-Lyt 2.2 antibody completely eliminated the suppressor cell activity, whereas anti-Lyt 1.2 partially, but significantly, reduced the suppressor cell activity. The suppressor cell, then, may be or may require a Lyt 1,2,3(+) cell with a relatively low density of the Lyt 1 antigen for activity. The Lyt phenotype of the IFNgamma- producing cells was examined for both virgin and suppressor cell populations. Treatment of cells with either anti-Lyt 1.2 or anti-Lyt 2.2 completely eliminated IFNgamma production in both virgin and suppressor cell cultures. Cocultivation of Lyt 1(+) and Lyt 2(+) cells in both virgin and suppressor cell cultures significantly restored the ability to produce IFNgamma when cells were stimulated with staphylococcal enterotoxin A. For the virgin cells, this seems to indicate clearly that both Lyt 1(+) and Lyt 2(+) cells are required for IFN production, but that Lyt 1,2,3(+) cells are not required. For the suppressor cell population this type of treatment resulted in IFNgamma production comparable to that of the virgin cell population. The treatment eliminated or depleted Lyt 1,2,3(+) cells from the suppressor cell population, thus providing additional evidence that a Lyt 1,2,3(+) cell is required for suppressor cell activity. Treatment of spleen cells with anti-Lyt antibodies at the time that they were involved in ongoing IFNgamma production showed that the IFNgamma-producing cell is Lyt 2(+). At least a 1:1 ratio of virgin to suppressor cells was required for optimal suppression of IFNgamma production by virgin spleen cells. This suggests that suppression involved cell-to-cell contact. Preliminary data showed that the suppressor cell activity could also be induced in in vitro cultures incubated with mitogen for 4 days. This is evidence that the suppressor cell is inducible and not necessarily recruited to the spleen from other lymphoid organs.