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A patient with preformed cytotoxic lymphocyte-dependent antibody (L.D.A.) against the specific renal transplant donor rapidly rejected the grafted kidney. The characteristics of rejection were not those of hyperacute rejection due to cytotoxic complement-dependent antibody or of acute rejection is attributed to the cytotoxic activity of L.D.A. The avoidance of transplants based on positive crossmatches by the L.D.A. test or at least the carrying out of the L.D.A. crossmatch is advised.

Biologically important regulatory mechanisms exist in many immune responses. The anatomic characteristics of lymphoid tissues and the cell-collaborative events exhibited in immune responses may be explicable in terms of potent regulatory phenomena rather than or as well as requirements for the initial activation of an immune response by antigen. Mechanistically, the regulatory web54 may be a series of Fc portion attachments to Fc receptors directed by the variable region specificities of the antibodies involved.

Low doses of irradiation, increased number of T cells, increased T cell activity as in the allogeneic effect, or early activation of an in vitro cell-mediated immune response all confer resistance to antibody feedback. In some of these systems, the resistance is directed against immunosuppression by intact IgG antibody whereas suppression by F(ab')2 antibody is either not changed or increased. These forms of interference with immunosuppression by antibody, are explained in terms of an Fc-dependent model for antibody-feedback regulation.

Fas (CD95)-mediated apoptosis in B and T cells is deficient in both human autoimmune lymphoproliferative syndrome and in MRL-lpr mice, a model for systemic lupus erythematosis (SLE). Autoimmune disease in these mice is associated with polyclonal B cell activation, increased serum immunoglobulin and autoantibodies. In non-autoimmune mice MHC class II is not required for normal serum immunoglobulin expression, and previously we have shown using MHC class II-deficient MRL-lpr mice (MRL-lpr Ab-/-) that generation of specific antibodies to DNA requires MHC class II directed T cell help. In contrast, in the present study we demonstrate that MRL-lpr Ab-/- mice also have a profound reduction of total serum immunoglobulin levels, suggesting abnormal polyclonal regulation of B cells by MHC class II-directed T cells occurs in the autoimmune MRL-lpr strain. This abrogation of immunoglobulin production does not occur in MHC class II-deficient non-obese diabetic (NOD) mice, nor in MHC class I-deficient NOD or MRL-lpr mice. Reduced immunoglobulin levels in MRL-lpr Ab-/- mice were not due to a lack of B cells or to an increased loss of circulating immunoglobulin, but were associated with reduced numbers of surface IgG-positive B cells. These results define a general abnormal regulation of B cells in MRL-lpr mice through a process requiring MHC class II, and suggest that Fas deficiency may allow expansion of totally T-dependent B cells. [ABSTRACT FROM AUTHOR]