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Subset-specific alterations in frequencies and functional signatures of γδ T cells in systemic sclerosis patients

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Abstract

Objective and design

Here, we evaluated the distribution and functional profile of circulating CD27+ and CD27− γδ T-cell subsets in systemic sclerosis (SSc) patients to assess their potential role in this disorder.

Materials and methods

Peripheral blood from 39 SSc patients and 20 healthy individuals was used in this study. The TCR-γδ repertoire, cytokine production and cytotoxic signatures of circulating γδ T-cell subsets were assessed by flow cytometry. Gene expression of EOMES, NKG2D and GZMA was evaluated by quantitative RT-PCR in both purified γδ T-cell subsets.

Results

Absolute numbers of γδ T-cell subsets were significantly decreased in SSc groups, likely reflecting their mobilization to the inflamed skin. Both γδ T-cell subsets preserved their relative proportions and Th1-type cytokine responses. However, cytotoxic properties showed significant disease-associated and subset-specific changes. SSc patients exhibited increased percentages of CD27+ γδ T cells expressing granzyme B or perforin and upregulated GZMA expression in diffuse cutaneous SSc. Conversely, EOMES and NKG2D were downregulated in both SSc γδ T-cell subsets vs. normal controls. Interestingly, patients with pulmonary fibrosis showed a biased TCR repertoire, with a selected expansion of effector Vγ9+ γδ T cells associated with increased frequency of cells expressing granzyme B, but decreased IFN-γ production.

Conclusions

Significant alterations on circulating γδ T-cell subsets suggest a deregulated (increased) cytotoxic activity and thus enhanced pathogenic potential of CD27+ γδ T cells in SSc.

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Acknowledgments

The authors thank the patients who took part in this study for their generous cooperation, Natacha Gonçalves-Sousa from Instituto de Medicina Molecular de Lisboa for her suggestions for improvement of the current manuscript and Bruno Marques and Ana Gonçalves for expert assistance in molecular studies.

A. Henriques has received grant support from the Faculty of Medicine, University of Coimbra.

Author information

Authors and Affiliations

  1. Faculty of Medicine, University of Coimbra, Coimbra, Portugal

    Ana Henriques, Cláudia Silva, Mariana Santiago, Maria João Henriques & José António Pereira da Silva

  2. Blood and Transplantation Center of Coimbra, Portuguese Institute of the Blood and Transplantation, Coimbra, Portugal

    Ana Henriques, António Martinho, Hélder Trindade & Artur Paiva

  3. Department of Biochemistry, University of Aveiro, Aveiro, Portugal

    Cláudia Silva

  4. Department of Rheumatology, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal

    Mariana Santiago, Maria João Henriques & José António Pereira da Silva

  5. Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal

    Bruno Silva-Santos

  6. Flow Cytometry Unit, Clinical Pathology Service, Centro Hospitalar e Universitário de Coimbra, Praceta Mota Pinto, Ed. S. Jeronimo, 3001-301, Coimbra, Portugal

    Artur Paiva

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  1. Ana Henriques
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  2. Cláudia Silva
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Correspondence to Artur Paiva.

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The authors declare that they have no conflict of interest.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Additional information

Responsible Editor: John Di Battista.

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Henriques, A., Silva, C., Santiago, M. et al. Subset-specific alterations in frequencies and functional signatures of γδ T cells in systemic sclerosis patients. Inflamm. Res. 65, 985–994 (2016). https://doi.org/10.1007/s00011-016-0982-6

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  • DOI: https://doi.org/10.1007/s00011-016-0982-6

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