Selective silencing of full-length CD80 but not IgV-CD80 leads to impairedclonal deletion of self-reactive T cells and altered regulation of immune responses

Co-stimulation provided by the B7 family of proteins underpins the developm ent of protective immunity. There are three identified members of this fami ly: CD80, its splice variant IgV-CD80 and CD86. It has hitherto been diffic ult to analyze the expression and function of IgV-CD80 since there are no a ppropriate reagents capable of distinguishing it from CD80. We have generat ed mice, by gene targeting, the lack CD80 whilst maintaining expression of IgV-CD80. Mutant animals did not delete T cells bearing mammary tumor virus -reactive LCR as efficiently as wild-type animals. We also demonstrate the importance of IgV-CD80 in the responses of recently activated cells and rev eal a role for CD80 in sustaining T cell responses. CD86, whilst critical t o primary T cell activation, made only a minor contribution to re-activatio n of normal cells.