TB and TT interactions involved in the regulation of human B cell differentiation were studied in vitro. The strategy employed here involved the isolation of OKT4+ and OKT8+ subsets and subsequent quantitative assessment of their effects on pokeweed mitogen (PWM) driven B cell differentiation as measured by the reverse hemolytic plaque assay. Thus, graded numbers of either untreated or irradiated OKT4+ and OKT8+ cell subsets were added to autologous B cells and after 6 days, cultures were assayed for plaque forming cells (PFC) activity. We found that the helper activity which is exclusively contained within the OKT4+ population is radiosensitive. Radioresistant OKT4+ helper cells could also be demonstrated but only at high T/B ratios. In contrast, the OKT8+ population is depleted of helper function and contains radiosensitive cells important in the suppression of B cell differentiation. However, the suppression observed with radiosensitive OKT8+ cells requires the presence of radiosensitive OKT4+ cells. Cooperative interactions between these subsets were further analyzed by investigating the immunoregulatory function of OKT4+ and OKT8+ cells in the induction of helper factor production in response to alloantigens. Evidence was obtained that the production of mixed lymphocyte culture (MLC) derived helper factor is dependent on OKT4+ cells but not OKT8+ cells. Furthermore, the alloantigen induced helper factor production and/or release was found to be suppressed by the radiosensitive OKT8+ subset. Finally, additional studies demonstrated that alloreactive as well as trinitrophenyl (TNP) altered-self reactive cytotoxic T lymphocytes (CTL) precursors are contained within the OKT8+ T cell subset. However, the killer cell activity was amplified by the presence of OKT4+ cells. This amplifying effect is mediated by factors released by OKT4+ cells after specific interaction with either soluble or alloantigens. These data, taken together, underscore the importance of functional TT interactions in the immunoregulation of both T and B cell differentiation.
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