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

Eur J Immunol. 2001 Jan;31(1):118-27. doi: 10.1002/1521-4141(200101)31:1<118::aid-immu118>3.0.co;2-x.

Abstract

Co-stimulation provided by the B7 family of proteins underpins the development of protective immunity. There are three identified members of this family: CD80, its splice variant IgV-CD80 and CD86. It has hitherto been difficult to analyze the expression and function of IgV-CD80 since there are no appropriate reagents capable of distinguishing it from CD80. We have generated 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 TCR as efficiently as wild-type animals. We also demonstrate the importance of IgV-CD80 in the responses of recently activated cells and reveal a role for CD80 in sustaining T cell responses. CD86, whilst critical to primary T cell activation, made only a minor contribution to re-activation of normal cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B7-1 Antigen / genetics
  • B7-1 Antigen / physiology*
  • CHO Cells
  • Clonal Deletion*
  • Cricetinae
  • Gene Targeting
  • Immunoglobulin Variable Region / physiology*
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mutation
  • RNA, Messenger / analysis
  • T-Lymphocytes / immunology*

Substances

  • B7-1 Antigen
  • Immunoglobulin Variable Region
  • RNA, Messenger