Recognition and response to alloantigens in vivo. II. Priming with accessory cell-depleted donor allogeneic splenocytes: induction of specific unresponsiveness to foreign major histocompatibility complex determinants.

Although the role of non-T, non-B Ia+ accessory cells as the cells that stimulate alloreactive T cells in vitro has been carefully examined, the capacity of such accessory cells to trigger host T cells in vivo has been considerably less well studied. Therefore, to address the latter issue, this investigation compared the ability of accessory cell-containing and accessory cell-depleted donor cells to mediate in vivo negative and positive selection of mixed lymphocyte reaction (MLR)-responsive peripheral blood lymphocytes (PBL). It was observed that both unseparated and accessory cell-depleted (Sephadex G-10-passed) allogeneic splenocytes, which expressed similar levels of Ia antigens as detected by flow cytometry, were equally efficient in inducing temporary specific unresponsiveness to alloantigens in host PBL 24 hr after donor cell injection. In contrast, 4 days after priming with unseparated major histocompatibility complex (MHC)-incompatible splenocytes, specific MLR hyperresponsiveness was detected in the PBL of these recipient mice, whereas specific hyporesponsiveness was consistently noted in animals injected with accessory-cell depleted splenocytes. PBL obtained from this latter group of mice continued to be specifically reduced in MLR proliferative capacity throughout the culture period and for at least 13 days after administration of accessory cell-depleted allogeneic splenocytes. Mixture of these MLR hyporesponsive and hyperresponsive PBL did not identify suppressor cells as responsible for the specifically lowered proliferative potential. These findings are discussed in the context of discrete signals required for T cell recognition and T cell activation.