Expression and function of CD80 and CD86 costimulator molecules on synovial dendritic cells in chronic arthritis.
OBJECTIVE
To examine CD86 expression on dendritic cells isolated from the synovial fluid (SFDC) of patients with chronic arthritis, and to determine the importance of both CD80 and CD86 molecules in SFDC-T lymphocyte interactions.


METHODS
CD86 messenger RNA (mRNA) and surface expression were analyzed in SFDC using reverse transcriptase-polymerase chain reaction and flow cytometry, respectively. The costimulator activity of the SFDC CD80 and CD86 molecules was determined by allogeneic mixed lymphocyte reaction (MLR). CD80 and CD86 induction on SFDC during in vitro culture was also examined.


RESULTS
Fresh SFDC either lacked or showed very weak surface expression of CD86 molecules (as shown previously for CD80), yet contained CD86 mRNA. CD80 antibodies minimally inhibited an allogeneic MLR, whereas CD86 antibodies and CTLA-4 Ig showed significant inhibition. Both CD80 and CD86 molecules were inconsistently induced on SFDC following culture in either media, interferon-gamma, or granulocyte-macrophage colony-stimulating factor.


CONCLUSIONS
SFDC may be defective antigen-presenting cells in vivo. The ability of CD80 and CD86 molecules to be induced and become functional on SFDC in vitro implies the presence of a negative regulatory compound(s) in the synovial environment.
Summers
K L
KL
Christchurch Hospital, New Zealand.
O'Donnell
J L
JL
Williams
L A
LA
Hart
D N
DN
D000069594:Abatacept; D015703:Antigens, CD / Q000235:genetics*; D000943:Antigens, Differentiation / Q000502:physiology; D015535:Arthritis, Psoriatic / Q000503:physiopathology*; D001172:Arthritis, Rheumatoid / Q000503:physiopathology*; D018122:B7-1 Antigen / Q000235:genetics*; D051940:B7-2 Antigen; D001483:Base Sequence; D018106:CD28 Antigens / Q000502:physiology; D060908:CTLA-4 Antigen; D002908:Chronic Disease; D003713:Dendritic Cells / Q000502:physiology*; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D018796:Immunoconjugates; D007166:Immunosuppressive Agents / Q000378:metabolism; D007959:Lymphocyte Culture Test, Mixed; D008562:Membrane Glycoproteins / Q000235:genetics*; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism; D013583:Synovial Membrane / Q000166:cytology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; C497964:CD86 protein, human; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D018796:Immunoconjugates; D007166:Immunosuppressive Agents; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D000069594:Abatacept