Subset-specific alterations in frequencies and functional signatures of γδ T cells in systemic sclerosis patients.
Inflamm Res
; 65(12): 985-994, 2016 Dec.
Article
en En
| MEDLINE
| ID: mdl-27576328
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 ANDMETHODS:
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.Palabras clave
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Bases de datos:
MEDLINE
Asunto principal:
Esclerodermia Sistémica
/
Subgrupos de Linfocitos T
Límite:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Inflamm Res
Asunto de la revista:
ALERGIA E IMUNOLOGIA
/
PATOLOGIA
Año:
2016
Tipo del documento:
Article
País de afiliación:
Portugal