Alloantigen-blocking antibodies in sera from highly sensitized uremic patients: antibody class and relationship with...

Previously, we identified an antimitogenic IgG antibody separated from sera of patients with known kidney transplant chronic rejection. This antibody inhibits individual patients' own unprimed T helper cell responses to alloantigens as well as a third-party mixed lymphocyte response, but does not inhibit autologous unprimed T helper cell proliferation to adherent anti-CD3 antibody. We suggest that the mechanism of inhibitory action is allogeneic-dependent.

We used a series of similar experimental designs to test the presence of this antibody in uremic, sensitized patients and have studied its relationship to sensitization as defined by the presence of lymphocytotoxins in four uremic groups: highly sensitized with or without previous graft loss, moderately sensitized with or without graft loss, nonsensitized without previous graft loss, and nonsensitized with graft loss.

(1) Sensitization is associated with the presence of a potent antibody that blocks primary mixed lymphocyte response. Primed cells are less susceptible to its antimitogenic action. (2) The blocking antibody activity is present only in sensitized patients who have IgG lymphocytotoxic activity against the same HLA class I antigens. (3) The blocking activity is unequal in the following order: IgG 3 > IgG 1 > IgG 2. (4) Although IgG 1 and 2 fractions contain lymphocytotoxic activity against HLA class I antigens, the IgG 3 fraction does not.

The differential effect of IgG antibodies on naive and memory T cells may explain why humeral responses to alloantigens can be maintained in the presence of blocking antibodies.