Background Systemic Sclerosis (SSc) is an autoimmune disease characterised by inflammation and extracellular matrix deposition. There are growing evidences of immune cells alterations, mainly in T cells subsets, including γδ T cells.

Objectives Evaluate the frequency of γδ T cells, their distribution among naïve, memory and effector functional compartments, the cytotoxic activity and γδ repertoire in SSc patients.

Materials and Methods The study enrolled 43 SSc patients, 30 of limited subtype (lSSc) and 13 of diffuse subtype (dSSc). Additionally 14% of the patients had less than 1 year since diagnosis, 49% ranging between 1 and 10 years and 37% with more than 10 years since diagnosis. The healthy control group (HG) included 20 age and gender matched individuals. The phenotypic and functional activity of γδ T cells was assessed by flow cytometry.

Results It was observed a lower frequency of γδ T cells in SSc patients compared to HG. Regarding the cytotoxic activity, it was verified a higher frequency of γδ T cells expressing granzime B and perforin in SSc group, particularly in lSSc, with a higher γδ T cells cytotoxic activity in patients with more than 10 years since the disease onset. Moreover, an increased frequency of γδ T cells with a naïve and effector phenotypes was observed in SSc group and these alterations were more evident in dSSc patients. Additionally, patients with pulmonary fibrosis demonstrated an increased frequency of effector memory and naïve γδ T cells closely associated to the decrease of central memory cells, when compared to patients without this clinical feature. Patients with more than 10 years since the disease onset, compared to those with less than 1 year since disease diagnosis, presented a higher frequency of effector cells associated to the decrease of central memory cells. Concerning γδ TCR repertoire assigned by Vδ2 and Vγ9 chains, it was observed in patients with SSc for more than 10 years, an increase of Vδ2^–Vγ9^– repertoire in naïve, central memory and effector γδ T cells when compared to patients with less than 1 year since diagnosis, which exhibit predominantly a Vδ2⁺Vγ9⁺ and Vδ2⁺Vγ9^– repertoire.

Conclusions Important alterations were observed in the frequency, cytotoxic activity, distribution among functional compartments and in γδ T cell receptor repertoire in peripheral blood γδ T cells that seem to be related to the time of disease after diagnosis or to clinical findings.