ICOS and B7 costimulatory molecule expression identifies activated cellular subsets in rheumatoid arthritis.
To better define important cell subsets expressing activation markers in rheumatoid arthritis (RA), we compared selective lymphocyte and monocyte B7H1, B7H2, B7RP.1, B7RP.2, and inducible costimulatory molecule (ICOS) expression from normal peripheral blood (NL PB), RA PB, and RA synovial fluid (SF) by multicolor flow cytometry and immunohistochemistry. RA SF memory lymphocytes expressed B7RP.1 and B7RP.2, suggesting that T-cells may function as antigen presenting cells (APCs) in RA joints. We found similar results for ICOS expression. RA SF CD14+ monocytes also expressed B7RP.1 (an ICOS ligand) and the homologous ligand B7RP.2, identifying monocytes as potential mediators of antigen processing and lymphocyte activation in RA. Furthermore, we found an increased population of RA SF CD14+ monocytes expressing B7H1 and B7H2. [The FACS analysis was supported by immunohistochemistry, showing intense lymphocyte and APC (macrophages with dendritic morphology) ICOS staining in RA synovial tissue (ST). Overall, these results define elevated populations of memoryT-lymphocytes expressing proinflammatory B7 molecules in RA SF that either stimulate T cells through ICOS (via ICOS ligands B7RP.1 and B7RP.2), or down-regulate RA ST T-lymphocytes through B7H1 and B7H2.] Therefore, in the same joint, there may exist positive and negative influences on the inflammatory response, and perhaps, the negative signals dominate as joint inflammation resolves.
Ruth
Jeffrey H
JH
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109-2200, USA. jhruth@umich.edu
Rottman
James B
JB
Kingsbury
Gillian A
GA
Coyle
Anthony J
AJ
Haines
G Kenneth
GK
Pope
Richard M
RM
Koch
Alisa E
AE
D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D018122:B7-1 Antigen / Q000378:metabolism*; D017252:CD3 Complex / Q000032:analysis / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007156:Immunologic Memory; D060889:Inducible T-Cell Co-Stimulator Protein; D017493:Leukocyte Common Antigens / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000032:analysis / Q000378:metabolism; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D009000:Monocytes / Q000378:metabolism; D013582:Synovial Fluid
D000945:Antigens, Differentiation, T-Lymphocyte; D018122:B7-1 Antigen; D017252:CD3 Complex; C556692:ICOS protein, human; D060889:Inducible T-Cell Co-Stimulator Protein; D018950:Lipopolysaccharide Receptors; D017493:Leukocyte Common Antigens