Mixed lymphocyte culture-lymphocyte-mediated cytotoxicity (MLC-LMC)* reactions by recipient spleen cells were strongly and specifically increased shortly after primarily vascularized heart grafts were placed in mice. Subsequently, in strain combinations in which eventual long-term graft survival occurred, the MLC-LMC became markedly suppressed, unlike the case in situations in which the recipients rejected their allografts. Unseparated spleen cells from long-term recipients are unchanged or slightly depressed in their in vitro MLC-LMC capacity. However, when splenocytes from the long-term B10.A recipients of BIO.BR heart grafts were depleted of Β cells and Lyt-2-positive cells, they were found to significantly enhance responses when added as third-party cells to MLC-LMC cultures. Similarly depleted splenocytes from naive mice were unaffected or depressed in their ability to contribute to this response as third-party cells. It was concluded that non-Ig-bearing, nonadherent Lyt 2+ lymphocytes from long-term heart graft recipient spleens were present that inhibited the responsiveness of other cells in these spleens.
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