The effect of prior activation history on subsequent responses of cloned T helper 1 (Th1) cells to TCR-mediated stimuli was examined. Th1 cells were maintained by stimulation with IL2 alone or by stimulation with specific antigen and APC in addition to IL2. Cells carried under both conditions proliferated equivalently in response to anti-CD3 antibody. However, anti-CD3 induced strong phosphatidyl inositol (PI) hydrolysis and increased [Ca++]i only in cells that had been maintained by stimulation with IL2 alone; cells that had been stimulated with specific antigen + APC gave neither PI nor Ca++ responses. The signaling pathways utilized by Th1 cells were thus influenced by prior stimulation through the TCR. Receptor-mediated activation was analyzed in T and B lymphocytes from normal mice and from mice infected with the MAIDS-inducing defective murine leukemia virus. Several weeks after viral infection, the proliferative responses of T and B cells to cross-linking of TCR and sIg respectively were significantly reduced despite the expression of normal surface levels of these receptors by most T and B cells. To analyze early signaling events in these cells, [Ca2+]i was measured in response to surface receptor cross-linking. The [Ca2+]i responses of both T and B cells from MAIDS-infected mice were decreased. B cell responses to sIg crosslinking were further analyzed by examining protein tyrosine phosphorylation induce by sIg cross-linking. It was found that after virus infection, there was a progressive loss of selected tyrosine phosphorylation events with conservation of other events. The response defect in B cells from MAIDS mice is thus reflected in selected alterations of tyrosine phosphorylation in response to sIg signaling.
