Prevention of lethal graft-versus-host disease in mice by monoclonal antibodies directed to T cells or their subsets. II. Differential effectiveness of IgG2a and IgG2b isotypes of anti-CD3 and anti-CD4 moAb

The effects of rat anti-CD3 and anti-CD4 moAb, of the IgG2a as well as of the IgG2b subclass, on the development of lethal graft-versus-host disease (GVHD) in a fully allogeneic mouse strain combination were compared in vivo. After treatment with these moAb, mice recovered from an initial loss of body weight. Moreover, their survival significantly improved. A single dose of 200 μg moAb resulted in a complete and long-term survival, which was not the case after treatment with anti-CD4 IgG2a moAb. A dose of at least 1 mg anti-CD4 IgG2a was necessary to induce a tolerant state. Mice effectively treated were fully repopulated with donor-type cells. Flow cytometric analysis of the recipient spleen cells demonstrated that the moAb caused depletion, modulation or coating of T cells or a combination of these. The moAb with the highest depleting capacity appeared to be anti-CD4 IgG2b moAb. Anti-CD3 IgG2a as well as IgG2b treatment resulted in a strong modulation of CD3 surface proteins, which was found on all days examined. Modulation of CD4 surface antigens did not occur in the case of anti-CD4 IgG2a moAb treatment. Anti-CD4 IgG2b moAb treatment, on the other hand, not only caused some CD4 modulation, but also, quite unexpectedly, a significant modulation of the CD3 molecule. Coating was only observed after treatment with anti-CD4 IgG2a moAb and lasted at least 1 week. In the first week after treatment no effect on the extent of coating or duration of coating of CD4+ T cells was found if the dose of anti-CD4 IgG2a moAb was increased from 200 μg to 1000 μg. These data provide further insight into anti-CD3 and anti-CD4 therapy in GHVD, thereby contributing to the development of effective therapeutic protocols in GVHD models.