Total threshold cytotoxicity of therapeutic antibodies for selective destruction of pathogenic memory T cells: implications for immunotherapy of autoimmune and allergenic disorders.

: Pathogenic memory CD4 T cells are the mainspring of autoimmune and allergic disorders, suggesting that effective pathogenetic immunotherapy should be primarily directed onto their direct inactivation without affecting normal cells. : A novel immunotherapeutic concept is proposed that applies suboptimal doses of several cytotoxic antibodies (Abs) against membrane antigens (Ags) (such as CD4, СD45RO, СD69, CD103, CD27, CD38, DR, etc.) with a view to achieve a threshold density of immune complexes on pathogenic memory CD4 T cells for their selective elimination. During disease exacerbations, a complex Ab formulation could be applied to combine Abs against CD4, СD45RO, and СD69 to selectively destroy both activated memory CD4 T cells located in lymphoid tissues and resident memory CD4 T cells present in local inflammatory sites in situ. In contrast, normal T cells are spared from destruction as being recognized only by some Abs leading to Ab-Ag complexes below cytolytic threshold levels. Inactivation of pathogenic CD4 T cells will also withdraw T helper support to pathogenic memory B cells and memory CD8 T cells, thus effectively diminishing their activity. : The described approach benefits from universality and potential availability of a vast library of monoclonal Abs with relevant specificity.