Role of gamma delta T cells in pathogenesis and diagnosis of Behcet's disease.
BACKGROUND
Behcet's disease (BD) is a multisystem disorder of unknown pathogenesis. The diagnosis is based on a set of international clinical criteria. Previous investigations have suggested that immunological cross-reactivity between peptides within streptococcal heat-shock proteins and human peptides might be involved in the pathogenesis of BD. We tested four peptides from mycobacterial heat-shock proteins to see if they specifically stimulated gamma delta T cells from BD patients. We then investigated this response to see whether it could be used as a laboratory test to diagnose BD.


METHODS
We used a T-cell proliferative test to assay responses to four mycobacterial 65 kDa heat-shock-protein peptides and to four homologous peptides derived from the sequence of the human 60 kDa heat-shock protein.


RESULTS
We elicited significant gamma delta T-cell responses to the mycobacterial peptides in 25 (76%) of 33 patients with BD, compared with 2 (3.6%) of 55 controls with recurrent oral ulcers, systemic disease, or no disorders. The proportion of BD patients who had false-negative results decreased if the test was done during clinical manifestation of disease activity. There was a correlation between disease activity and T-cell responses. Four homologous peptides from human 60 kDa heat-shock protein also specifically stimulated T cells from patients with BD but with lower stimulation indices.


CONCLUSIONS
Activation of peripheral-blood mononuclear cells with the four heat-shock-protein peptides elicited significant T-cell proliferative responses by the gamma delta subset of T cells, which may regulate alpha beta T cells. Because these peptides have a high specificity for BD, this assay can be used as a laboratory diagnostic test for BD.
Hasan
A
A
Department of Immunology, United Medical and Dental Schools of Guy's Hospital, London, UK.
Fortune
F
F
Wilson
A
A
Warr
K
K
Shinnick
T
T
Mizushima
Y
Y
van der Zee
R
R
Stanford
M R
MR
Sanderson
J
J
Lehner
T
T
D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology*; D001528:Behcet Syndrome / Q000175:diagnosis* / Q000276:immunology*; D016022:Case-Control Studies; D002455:Cell Division; D002469:Cell Separation; D002648:Child; D005260:Female; D005434:Flow Cytometry; D006360:Heat-Shock Proteins / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D009163:Mycobacterium bovis / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D015854:Up-Regulation
D000942:Antigens, Bacterial; D006360:Heat-Shock Proteins; D016692:Receptors, Antigen, T-Cell, gamma-delta