Role of gamma delta T cells in pathogenesis and diagnosis of Behcet's disease

Lancet. 1996 Mar 23;347(9004):789-94. doi: 10.1016/s0140-6736(96)90868-5.


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.

Findings: 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.

Interpretation: 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.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Antigens, Bacterial / immunology*
  • Behcet Syndrome / diagnosis*
  • Behcet Syndrome / immunology*
  • Case-Control Studies
  • Cell Division
  • Cell Separation
  • Child
  • Female
  • Flow Cytometry
  • Heat-Shock Proteins / immunology*
  • Humans
  • Lymphocyte Activation / immunology
  • Male
  • Mycobacterium bovis / immunology
  • Receptors, Antigen, T-Cell, gamma-delta / immunology*
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology*
  • Up-Regulation


  • Antigens, Bacterial
  • Heat-Shock Proteins
  • Receptors, Antigen, T-Cell, gamma-delta