Combinatorial functions of two chimeric antibodies directed to human CD4 and one directed to the α-chain of the human interleukin-2 receptor

Abstract

SUMMARYThe general feasibility of chimerization of monoclonal antibodies (mAbs) has already been shown for a large number of them. In order to evaluate in vitro parameters relevant to immunosuppressive therapy, we have chimerized and synthesized two anti-CD4 mAbs recognizing two different epitopes on the human T-lymphocyte antigen, CD4. The chimerized mAbs are produced at levels corresponding to those of the original hybridoma cell lines. With respect to activation of human complement, the individual Abs are negative; however, when used in combination, complement activation was performed. When applied in combination, they were found to modulate the CD4 antigen, whereas the individual mAb do not display this property. Individually they mediate an up to 60% inhibition of the mixed lymphocyte reaction (MLR). However, by combination of an anti-CD4 mAb with one directed against the a-chain of the human IL2 receptor, nearly 100% inhibition of the MLR was achieved, even with reduced dosage of the mAbs. Our data suggest that the combination of an anti-CD4 mAb and an anti-IL2Rcc chain mAb is more effective with respect to immunosuppression than each mAb by itself, indicating that this mAb cocktail could be a new strategy for immunosuppressive therapy.

Impairment of CD4+CD25+ regulatory T-cells in autoimmune liver disease

“…A marked increase of CD25þ lymphocytes has been described in a variety of autoimmune disorders, including autoimmune hepatitis, type 1 diabetes and lupus nephritis [39][40][41], particularly at diagnosis or during phases of high disease activity. This has led to the proposal of using anti-CD25 monoclonal antibody to prevent or treat these conditions [41][42][43]. Indeed, the use of anti-CD25 monoclonal antibody prevents immune diabetes in the BB rat [44].…”