Role of γδ T cells in pathogenesis and diagnosis of Behçetʹs disease

Background Behçetʹs 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 crossreactivity 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 γδ 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. Findings We elicited significant γδ 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. Interpretation Activation of peripheral-blood mononuclear cells with the four heat-shock-protein peptides elicited significant T-cell proliferative responses by the γδ subset of T cells, which may regulate αβ T cells. Because these peptides have a high specificity for BD, this assay can be used as a laboratory diagnostic test for BD.