Regulation of immunoglobulin production after human marrow grafting. The role of helper and suppressor T cells in acute graft-versus-host disease.

The effect of acute graft-versus host disease (GVHD) on T4 and T8 lymphocyte regulation of in vitro immunoglobulin production was explored. The peripheral blood lymphocytes from 20 patients were studied sequentially in the first 100 days after sibling bone marrow grafting for hematologic malignancy or aplastic anemia. T and non-T lymphocytes were prepared from peripheral blood by Ficoll-Hypaque density gradient centrifugation and sheep erythrocyte rosetting. T cells were enriched for T4 or T8 cells and cocultured for six days with pokeweed mitogen and autologous non-T or T and non-T cells from unrelated normal individuals. Immunoglobulin production was assessed using a reverse hemolytic plaque assay. All three patients without acute GVHD had failure of non-T cells to secrete immunoglobulin, one had failure of helper T cell activity, and 2 developed suppressor T cells. Similarly, all six patients studied sequentially after the development of GVHD had non-T-cell failure, five developed helper T cell failure, and five had suppressor T cells. These data suggest no difference in lymphocyte function before or after the development of acute GVHD. When the T cells of these patients were split into T4 and T8 subpopulations and studied for immunoglobulin production there was helper T cell failure in 4 of 9 tests with enriched T4 populations. Five of 9 tests with T8 enriched populations showed suppressor activity. Suppressor T cell function was also seen in 4 of 9 tests with with T4-enriched populations. These data show that T cell function does not necessarily correlate with the surface phenotype during the first 100 days after grafting. A role for cytomegalovirus (CMV) infection in bringing out suppressor activity is suggested, because among patients without GVHD, 6 of 8 tests in CMV-positive patients showed suppressor cells compared with none of 4 tests in patients without CMV infection.