Thymic stromal cells induce hapten-specific, genetically restricted effector suppressor cells in vivo

Thymic stromal cells (TSC) from CKB (H-2k) and B10.BR (H-2k) mice were cultured to examine if these cell populations would induce suppressor cell responses. I-A molecules were not detected on the surface of TSC, however, following incubation of these cells with recombinant interferon (IFN)-gamma, I-A antigens were induced. Non-specific esterase activity was seen in 5% of the cultured B10.BR cells but was absent in CKB derived cultures. Morphologically, both CKB and BR-TSC populations lacked an epithelial ultrastructure and cytokeratin immunoreactivity, hence were mesenchymal. As there was no evidence of surface Mac-1 and 33D1 molecules, these cells were not of macrophage or dendritic cell lineage. Both B10.BR and CKB TSC cells (1 x 10(4] induced effector suppressor cells when chemically conjugated with the hapten, NP-O-Succinamide (NP) and injected subcutaneously into syngeneic mice. The suppression by transferred lymph node cells was not always present when TSC were cultured in medium without IFN-gamma, but after incubation with IFN-gamma for 4 days, a significant suppression was consistently evident. Genetically restricted induction of suppressive activity was noted when the I-J-congenic strains of mice, B10.A (5R) and B10.A (3R), were used as the lymph node donors; suppressor cells generated in 5R (I-Jk) mice, significantly suppressed the syngeneic response, whereas in the 3R (I-Jb) strain, there was no significant suppression. The suppression was hapten-specific and depended on both the number of TSC and the dose of IFN-gamma. All these data taken together suggest that, although the TSC used in this study appears to be a mixture of heterogeneous cell populations from the thymic stroma, TSC are capable of inducing hapten-specific, genetically restricted effector suppressor cells when IFN-gamma is included in the culture system.