Relationship between disease severity and responses by blood mononuclear cells from patients with rheumatoid arthritis to human heat-shock protein 60.
The hypothesis that T-cell responses to the 60 000 MW family of heat-shock proteins (hsp) may be related to the severity of rheumatoid arthritis (RA) was examined. Peripheral blood mononuclear cells (PBMC) from most normal individuals and both early and established RA patients proliferated in vitro in response to human hsp 60 and mycobacterial hsp 65 as well as tetanus toxoid (TT) and mycobacterial purified protein derivative (PPD). PBMC from some patients with established RA gave responses to hsp 60 that were above the normal range and/or peaked earlier than PBMC from normal individuals. The responses of PBMC from established RA to hsp 65, but not PPD or TT, were also higher than those from normal individuals, but the peak responses to all three antigens appeared delayed. Thus a selective increase in responsiveness to hsp 60 develops with disease duration in many RA patients. Six assessments of disease activity and severity were made but apart from rheumatoid factor titre, they were unrelated to the proliferative response. Similarly, disease activity and severity did not differ between those RA patients whose hsp 60 stimulated cells produced interferon-gamma and those who did not, although patients whose hsp 60-stimulated T cells produced interleukin-4 (IL-4) and/or IL-10, appeared to have less disease activity and severity than those who did not. Significant negative correlations were found between IL-10 production by hsp 60-stimulated cells and disease assessments. It is considered that RA is less severe in those patients whose hsp 60-stimulated cells produce T-helper 2 type cytokines.
MacHt
L M
LM
Departments of Pathology & Microbiology, University of Bristol, Department of Medicine, University of Cambridge, and Peptide Therapeutics plc, Cambridge, UK.
Elson
C J
CJ
Kirwan
J R
JR
Gaston
J S
JS
Lamont
A G
AG
Thompson
J M
JM
Thompson
S J
SJ
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001426:Bacterial Proteins; D018929:Cell Culture Techniques; D002455:Cell Division / Q000276:immunology; D018834:Chaperonin 60 / Q000276:immunology*; D018833:Chaperonins / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index
D001426:Bacterial Proteins; D018834:Chaperonin 60; D016207:Cytokines; C074119:heat-shock protein 65, Mycobacterium; D016753:Interleukin-10; D018833:Chaperonins