Monoclonal anti-T cell (T12) antibody treatment of graft-versus-host disease in severe combined immunodeficiency: targeting of antibody and activation of complement on CD8+ cytotoxic T cell surfaces.

Abstract

We report a 6-month-old male child with severe combined immunodeficiency who received an unirradiated blood transfusion and developed acute, severe graft-versus-host disease (GVHD), for which he received monoclonal anti-T cell (anti-T12) antibody treatment. The GVHD was manifested by a confluent maculopapular rash and increased liver function tests and was documented by skin biopsy. Separation of peripheral blood mononuclear cells forming rosettes with sheep red blood cells revealed engrafted T cells having the nonrelated HLA type of the blood donor. The patient was treated with intravenous monoclonal anti-T12 in a dose of 0.3 mg/kg/day for 5 days. An in vivo effect of the anti-T12 was suggested by clinical improvement of his skin rash and return of the liver transaminases to the normal range. Moreover, human complement components, activated C3 and C4, were detected by fluorescence microscopy on the surfaces of the engrafted CD8+ lymphocytes on the skin biopsy specimens. Also, with a biotin-avadin assay, the presence of the anti-T12 was detected on these same cells. These studies document not only the in vivo targeting of monoclonal anti-T12 antibody to cytotoxic T cells producing GVHD but also the activation of complement on these cells.