Inflammatory cytokines IFN-gamma plus TNF-alpha induce regulated expression of CD80 (B7-1) but not CD86 (B7-2) on murine fibroblasts.
Optimal T cell activation requires signals delivered via both the TCR and the costimulatory receptors. Considerable experimental data now suggest that this costimulatory signal is generated predominantly by CD28 when engaged by its ligands CD80 (B7-1) and/or CD86 (B7-2). Whether T cell activation is controlled in part by regulated CD80 and/or CD86 expression has been incompletely explored. Here, we report that CD80 can be expressed constitutively by murine fibroblasts and up-regulated after treatment with IFN-gamma plus TNF-alpha. CD80 expression and function was confirmed by 1) Northern analysis, 2) specific immunoprecipitation of a approximately 69-kDa surface protein that comigrated with CD80 precipitated from CD80-transfected CHO cells, and 3) two independent assays for costimulation of Ag-specific T cell activation. Taken together, these observations suggest that CD28/CTLA-4 ligands are expressed on a wider variety of tissues than previously suspected and that their expression is dynamically regulated. Consequently, these results might explain previous observations that inflammatory cytokines can result in autoimmune responses.
Pechhold
K
K
Immune Cell Biology Program, Naval Medical Research Institute, Bethesda, MD 20889, USA.
Patterson
N B
NB
Craighead
N
N
Lee
K P
KP
June
C H
CH
Harlan
D M
DM
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D015703:Antigens, CD / Q000378:metabolism*; D018122:B7-1 Antigen / Q000378:metabolism*; D051940:B7-2 Antigen; D002478:Cells, Cultured; D004357:Drug Synergism; D005347:Fibroblasts / Q000276:immunology*; D005434:Flow Cytometry; D015870:Gene Expression; D007371:Interferon-gamma / Q000008:administration & dosage*; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage*; D015854:Up-Regulation
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma