Mycobacteria and human heat shock protein-specific cytotoxic T lymphocytes in rheumatoid synovial inflammation.
OBJECTIVE
To study the cytotoxic capacity of mycobacteria-specific T lymphocyte lines and clones from sites of inflammation in patients with rheumatoid arthritis (RA). We also studied antigen specificity, surface phenotype, expression of T cell receptors (TCR), and HLA restriction.


METHODS
Autologous macrophages (M phi) from the synovial membrane (SM), synovial fluid (SF), or peripheral blood (PB) were used as target cells in cytotoxicity assays.


RESULTS
All SM and SF cell lines tested thus far have shown specific lysis of the autologous M phi from SM or PB that had been pulsed with BCG (bacillus Calmette-Guerin), but no cytotoxicity when the targets were pulsed with irrelevant antigens such as tetanus toxoid and Chlamydia. Both CD4+ and CD8+ cells were shown to be involved in the specific cytolysis. The majority of the cytotoxic T lymphocyte (CTL) lines were TCR alpha/beta + cells. However, both TCR alpha/beta + and TCR gamma/delta + clones (TCR delta 1+) from one RA patient showed antigen-specific lysis. Antigen-specific recognition by a number of CTL lines and clones generated from SF and SM was restricted by HLA-DR molecules. Two Mycobacterium bovis 65-kd heat shock protein (HSP)-specific TCR alpha/beta + SF T cell clones also lysed M phi that had been pulsed with a recombinant human 65-kd HSP.


CONCLUSIONS
Joint inflammation and destruction might be partly attributable to a cross-reaction of mycobacteria-induced cytotoxic T cells with self HSP.
Institute of Immunology and Rheumatology, University of Oslo, Norway.
S G
SG
Li
A J
AJ
Quayle
Y
Y
Shen
J
J
Kjeldsen-Kragh
F
F
Oftung
R S
RS
Gupta
J B
JB
Natvig
O T
OT
Førre
D000911:Antibodies, Monoclonal; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000150:complications / Q000473:pathology; D001500:BCG Vaccine / Q000494:pharmacology*; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D000939:Epitopes; D005260:Female; D006681:HLA-D Antigens / Q000502:physiology; D006360:Heat-Shock Proteins / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D010641:Phenotype; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis; D013582:Synovial Fluid / Q000276:immunology; D013583:Synovial Membrane / Q000276:immunology; D013585:Synovitis / Q000209:etiology / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000911:Antibodies, Monoclonal; D001500:BCG Vaccine; D000939:Epitopes; D006681:HLA-D Antigens; D006360:Heat-Shock Proteins; D008565:Membrane Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta