Expansion of γδ T-cells in Behçet's disease: Role of disease activity and microbial flora in oral ulcers

doi:10.1067/mlc.2003.1

Journal of Laboratory and Clinical Medicine

Volume 141, Issue 1, January 2003, Pages 33-40

https://doi.org/10.1067/mlc.2003.1 Get rights and content

Abstract

γδ T-cells participate in the immune response to infections and in autoimmunity by recognizing bacteria-derived and autologous antigens. The goal of this study was to evaluate the involvement of γδ T-cells in Behçet's disease (BD). γδ T-cells in the peripheral-blood mononuclear cells (PBMCs) of Israeli patients with definite BD (n = 23), normal controls (n = 16), and patients with familial Mediterrranean fever (FMF; n = 20) were evaluated by means of flow cytometry. The responses of patient and control γδ T-cells to medium conditioned by microorganisms cultured from an oral ulcer of a patient with active BD were compared. The proportions of CD3⁺ and CD8⁺ cells in the PBMCs were not significantly different between groups. In contrast, γδ-T-cells accounted for 7.01% ± 4.42% of the PBMCs in BD compared with 3.56% ± 3.45% in FMF (P <.005) and 3.7% ± 3.15% in normal individuals (P <.009). Their numbers were significantly higher during active disease than in remission (9.45% ± 5.08% versus 2.27% ± 3.3%; P <.009). The number of T-cell-receptor γδ⁺ and Vδ2⁺ cells of BD patients, but not of controls, increased after 96 hours of culture in medium containing supernatant of microorganisms cultured from an oral ulcer in a patient with BD relative to their proportions in control medium: 58.2% vs 13.9% (P <.05) and 28% vs 9% (P <.04), respectively, of the cultured T-cells (n = 4).γδ T-cells are expanded in BD PBMCs during active disease. An exaggerated proliferative response to products released by microorganisms present in oral ulcers may play a role in this phenomenon. (J Lab Clin Med 2003;141:33-41)

Section snippets

Determination of T-cell antigens

PBMCs were isolated from heparinized blood by means of Ficoll-Hypaque (Sigma Chemical, St. Louis, Mo) density centrifugation.¹⁶ To detect surface-membrane antigens, we spun down 0.5 to 1 × 10⁶ cells in 5-mL glass tubes in PBS solution (pH 7.4). Resuspended pellets were stained directly with mAb directly conjugated with fluorochromes or with saturating concentrations of primary murine mAb at 4°C for 30 minutes and washed twice in PBS and 0.2% sodium azide. FITC-conjugated goat anti-mouse Ig

T-cell subsets in PB

We compared the percentages of CD3⁺, CD8⁺, and γδ TCR⁺ cells in the PBMCs of patients with BD (n = 23) and with FMF (n = 20), as well as in the normal controls (n = 18). As shown in Fig 1, CD3⁺ cells constituted 60.58% ± 16.15%, 56.93% ± 14.7%, and 60.34% ± 14.89% of the PBMCs, respectively, whereas CD8⁺ cells accounted for 25.6% ± 8.01%, 23.1% ± 8.6%, and 21.9% ± 12.8% of the PBMCs, respectively.

. Distribution of T-cell subsets in PB. Each data point represents a single individual in each group.

Discussion

The results of these experiments confirm and expand those reported from Japan, Turkey, and Great Britain with regard to activation of the γδ T-cell subset in BD.19, 20, 21, 22 Thus a significant increase in the percentage of these cells among the PBMCs of Israeli BD patients relative to both normal individuals and patients with FMF was detected. Moreover, our results demonstrate that the increase in γδ T-cells is related to disease activity and that products of microorganisms from oral

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Citation Excerpt :
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^☆: Reprint requests: Ilan Bank, MD, Department of Medicine, Chaim Sheba Medical Center, Tel Hashomer 52621, Israel; e-mail: [email protected].

^☆☆: 0022-2143/2003 $30.00 + 0

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Original ArticlesExpansion of γδ T-cells in Behçet's disease: Role of disease activity and microbial flora in oral ulcers☆,☆☆

Abstract

Section snippets

Determination of T-cell antigens

T-cell subsets in PB

Discussion

Lancet

Hum Immunol

Lancet

J Allergy Clin Immunol

Immunity

Int J Oral Maxillofac Surg

Behçet's disease

N Engl J Med

Behçet's disease in Japan and in Great Britain: a comparative study

Ocul Immunol Inflamm

Epidemiology of Adamantiades-Behçet's disease

Ann Med Interne (Paris)

Immunopathogenesis of Behçet's disease

Ann Med Interne (Paris)

Association analysis between the MIC-A and HLA-B alleles in Japanese patients with Behçet's disease

Arthritis Rheum

Significant associations of HLA-B*5101 and B*5108, and lack of association of class II alleles with Behçet's disease in Italian patients

Tissue Antigens

Lack of association of MICA transmembrane region polymorphism and Behçet's disease in Spain

Tissue Antigens

T cell responses to 60/65 kDa heat shock protein derived peptides in Turkish patients with Behçet's disease

J Rheumatol

γδ and other unconventional T lymphocytes: What do they see and what do they do?

Proc Natl Acad Sci U S A

Original Articles
Expansion of γδ T-cells in Behçet's disease: Role of disease activity and microbial flora in oral ulcers☆,☆☆

Significant associations of HLA-B5101 and B5108, and lack of association of class II alleles with Behçet's disease in Italian patients