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Annals of the Rheumatic Diseases logoLink to Annals of the Rheumatic Diseases
. 2002 May;61(5):438–443. doi: 10.1136/ard.61.5.438

γδ T cell subsets in patients with arthritis and chronic neutropenia

I Bank, L Cohen, M Mouallem, Z Farfel, E Grossman, A Ben-Nun
PMCID: PMC1754096  PMID: 11959768

Abstract

Background: An abnormal distribution of subsets of γδ T cells, which are a component of the inflammatory infiltrate in arthritic synovium, has been demonstrated in the peripheral blood (PB) of patients with arthritis and neutropenia.

Objective: To evaluate whether the clinical manifestations of patients with arthritis and neutropenia are related to the specific γδ T cell subset predominant in the PB.

Methods: Flow cytometry of PB lymphocytes in six consecutive patients with chronic neutropenia and arthritis was performed. Variable (V) γ and δ gene families were analysed by polymerase chain reaction. cDNA was subjected to direct automated sequencing of T cell receptor (TCR) genes.

Results: Three patients had non-deforming and non-erosive rheumatoid factor (RF)+ polyarticular rheumatoid arthritis, RF+ oligoarticular arthritis, or RF- non-deforming oligoarticular psoriatic arthritis with persistent expansions of Vγ1+/Vδ2+, Vγ2+/Vδ2+, or Vγ1+/Vδ undetermined (2- 1-) T cells, respectively. The other three patients, without persistent expansion of γδ T cells, had either non-deforming and non-erosive oligo- or polyarthritis with a balanced distribution of several Vδ and Vγ genes, or severe erosive RF+ arthritis with deficiency of all but Vγ1+/Vδ1+ T cells.

Conclusions: γδ T cell lymphoproliferations in chronic neutropenia and arthritis use different Vγ and Vδ gene families, often forming T cell receptor (TCR) structures that are infrequent in normal adult PB. Arthritis with Vγ1+/Vδ2+, Vγ2+/Vδ2+, or Vγ1+/Vδ2-/Vδ1- γδ T cells in the PB is non-deforming and non-erosive, suggesting a protective effect of these cells, as opposed to a more pathogenic contribution of Vγ1+/Vδ1+ cells.

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Figure 1 .

Figure 1

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Analysis of T cell subsets in patient PBL. FACS analysis of patient PBL with mAb directed against the indicated antigens. Percentages of the indicated subsets are shown.

Figure 2 .

Figure 2

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Vδ genes in patient PB. Southern blot representing DNA fragments amplified from PBL. PCR was employed using 5` Vδ gene family specific primers (Vδ1, Vδ2, and Vδ3 corresponding to lanes 1, 2, and 3) matched to Cδ gene specific primers.

Figure 3 .

Figure 3

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(A) Vγ TCR gene amplification in clone B8. Each lane represents hybridisation with a Vγ family specific probe, after amplification with family specific Vγ primers as indicated and a 3` Cγ primer. (B) Nucleic acid and deduced amino acid sequence of patient 1 TCRδ genes. CδVδ2 amplified cDNA segments prepared from clone B8 and non-selected patient 1 PBL were sequenced in the 5` and 3` directions by the automated DNA sequencer ("Patients and methods"). The 5` and the 3` sequences were aligned and junctional sequences confirmed. The resulting matching sequences are aligned. The sequence has an in-frame Vδ2Dδ2Jδ1Cδ rearrangement and N region diversity. The deduced amino acid sequences are given below the nucleotide sequences.

Figure 4 .

Figure 4

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Vγ TCR gene amplification in PBL. Each lane represents hybridisation with a family specific Vγ probe, after amplification with a family specific 5` Vγ primer and a 3` Cγ primer. Five different Vγ primers (detecting Vγ1.2 in lane 1, Vγ1.2 and 1.4 in lane 2, Vγ1–1.8 in lane 3, Vγ1.8 in lane 4, and Vγ2 in lane 5) were used.

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