Cellular and Humoral Response to Transplantation Antigens I. Development of Alloantibody-forming Cells and Cytotoxic Lymprocytes

I t is generally accepted that the graft-versus-host (GVH) 1 reaction represents an immunological phenomenon called forth by the introduction of immunocompetent cells into a host carrying different transplantation antigens and incapable of rejecting the grafted cells (1, 2). Despite numerous studies, the actual mechanisms of the GYH reaction are poorly understood and, although there is ample evidence that some of the grafted cells proliferate and differentiate in the recipient lymphoid organs (3), no attempt has been made to assess their relative significance. Previous in vitro studies have shown that transplantation immunity in mice is characterized by the development of at least two types of effector cells, namely cells which produce and release alloantibody, and cells which display a cytotoxic activity against target cells carrying the sensitizing alloantigens (4). The present study was undertaken to determine whether similar effector cells also appeared during the GVH reaction. Advantage was taken of the availability of two in vitro assay systems allowing the independent detection of lyric alloantibody plaque-forming cells (PFC) and of cytotoxic lymphocytes (CL) using the same target cells (5-7). I t was found that both types of effector cells were present in spleens of heavily-irradiated mice injected 4-5 days earlier with allogeneic spleen cells. Specificity studies indicated that the effector cells were of the donor genotype and were specifically sensitized against the host alloantigens. Clear evidence for a different origin of alloantibody PFC and CL was obtained by studying their susceptibility to treatment with anti~-serum.