Reactivity of gamma/delta T cells to human 60-kd heat-shock protein and their cytotoxicity to aortic endothelial cells in Takayasu arteritis.
OBJECTIVE
Increased numbers of circulating gamma/delta T cells with a restricted T cell receptor repertoire, as well as colocalization of the expression of heat-shock protein Hsp60/65 and gamma/delta T cells in the arterial lesions of patients with Takayasu arteritis (TA), indicate that gamma/delta T cells may react to Hsp60 and cause damage to the arterial endothelium. In this study we investigated the proliferative responses of gamma/delta T cells to human Hsp60 and their cytotoxicity to human aortic endothelial cells (ECs) in patients with TA.


METHODS
Blood samples were obtained from 12 patients with TA, 8 patients with systemic lupus erythematosus (SLE) (as disease controls), and 10 healthy control subjects. Proliferative responses of circulating gamma/delta T cells to human Hsp60 were detected by flow cytometry-based bromodeoxyuridine incorporation assay. Cytotoxicity of the gamma/delta T cells to human aortic ECs was analyzed by colorimetric lactate dehydrogenase release assay.


RESULTS
The gamma/delta T cells of 11 of 12 patients with TA exhibited reactivity to Hsp60, whereas none of the gamma/delta T cells from patients with SLE or healthy controls showed reactivity (both P < 0.001). The mean +/- SD proliferative response of gamma/delta T cells in patients with TA was 21.4 +/- 11.3%, compared with 4.2 +/- 1.2% in patients with SLE and 4.01 +/- 1.82% in healthy controls (both P < 0.001). In addition, compared with the control groups, the gamma/delta T cells of patients with TA had increased spontaneous cytotoxicity to aortic ECs (22.1 +/- 15.0% versus 9.6 +/- 2.13% in SLE patients and 8.1 +/- 4.7% in healthy controls; both P < 0.005), which was further enhanced following stimulation of gamma/delta T cells with Hsp60. The cytotoxicity of the gamma/delta T cells was significantly inhibited by treatment of these cells with concanamycin A and anti-Fas ligand-blocking antibodies.


CONCLUSIONS
The results show that gamma/delta T cells in patients with TA are reactive to Hsp60 and exhibit cytotoxicity to aortic ECs, suggesting a key role of Hsp60 and gamma/delta T cells in the pathogenesis of TA.
Department of Hematology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow-226014, India.
Sunil Kumar
SK
Chauhan
Mahavir
M
Singh
Soniya
S
Nityanand
D000293:Adolescent; D000328:Adult; D001011:Aorta / Q000276:immunology* / Q000473:pathology; D049109:Cell Proliferation; D002469:Cell Separation; D002478:Cells, Cultured; D018834:Chaperonin 60 / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D004730:Endothelium, Vascular / Q000276:immunology / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D013625:Takayasu Arteritis / Q000276:immunology*
D018834:Chaperonin 60; D016692:Receptors, Antigen, T-Cell, gamma-delta