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.
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.
Bugeon
L
L
Department of Biology, Imperial College of Science Technology and Medicine, London, GB. l.bugeon@ic.ac.uk
Hargreaves
R E
RE
Crompton
T
T
Outram
S
S
Rahemtulla
A
A
Porter
A C
AC
Dallman
M J
MJ
D000818:Animals; D018122:B7-1 Antigen / Q000235:genetics / Q000502:physiology*; D016466:CHO Cells; D017637:Clonal Deletion; D006224:Cricetinae; D018390:Gene Targeting; D007135:Immunoglobulin Variable Region / Q000502:physiology*; D008213:Lymphocyte Activation; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009154:Mutation; D012333:RNA, Messenger / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology*
D018122:B7-1 Antigen; D007135:Immunoglobulin Variable Region; D012333:RNA, Messenger