Horst Dieter Prof Schlumberger

A new model for investigations of t-cell functions in mice: differential immunosuppressive effects of two monoclonal anti-thy-1.2 Antibodies.

Two monoclonal anti-Thy-1.2 antibodies were investigated for their activity in eliminating T cells in vitro and in vivo. Both antibodies exert a complement-dependent cell cytotoxicity in vitro. Antibody B that belongs to the IgM class shows a 100-fold higher complement-dependent cytotoxic activity than antibody C, which is of IgG2a class. However, administration of antibody C into Balb/c mice results in the elimination of T cells as determined by the failure of different T-cell functions. Within 24 hours after administration of antibody C, the reactivity of spleen of lymph-node cells to T-cell mitogens, the antibody response to the T-cell-dependent antigen SRBC and the SRBC-induced delayed-type hypersensitivity are completely abolished. These effects are dose-dependent in a dose range of 0.1-1.0 mg Ig protein per animal and affects only T cells in the peripheral lymphoid organs. The Thy-1.2-bearing cells residing in the thymus are not impaired by the treatment of the animals with this monoclonal antibody and are able to repopulate the peripheral lymphoid organs within 30 to 60 days. Investigations into the mode of action of the removal of peripheral T cells revealed that antibody-C-coated Thy-1.2-bearing cells are rapidly phagocytosed by macrophages, while antibody-B-coated Thy-1.2-bearing cells are not. This might be the reason for the differential in-vivo activities of the two monoclonal antibodies. A model with new qualities for the study of functions and the regeneration of T cells in vivo has been established.