Attenuation of autoimmune disease and lymphocyte accumulation in MRL/<i>lpr</i> mice by treatment with anti‐Vβ8 antibodies

Abstract MRL‐MP‐lpr/lpr mice are afflicted by a severe systemic autoimmune disease that is aggravated by the lpr mutation resulting in the accumulation of phenotypically abnormal lpr cells (CD3 + CD4 − CD8 − ) in all lymphoid issues including hyperplastic lymph nodes. Given that products of the T cell receptor Vβ8 gene family are overrepresented among lpr cells, different schedules aimed at selectively decreasing the frequency of lpr cells were designed. First, continuous administration of the monoclonal antibody F23.1 (specific for Vβ8 products) resulted in a significant depletion of Vβ8 + cells and prevented the manifestation of lymph accumulation at the same time as it reduced the serological, clinical, and histopathological signs of autoimmune disease. Along the same line, administration of either F23.1 or two different anti‐F23.1 anti‐idiotypic antibodies to MRL/Mp‐lpr/lpr mothers elicited, in the offspring, the production of antibodies sharing a recurrent idiotype with F23.1 and resulted in long‐term amelioration of autoimmunity and lymphadenopathy. Thus, a strategy aimed at specifically reducing the frequency of a subset of lpr cells proved successful in mitigating the autoimmune process.