Abnormal Distribution of Gamma-Delta T Lymphocytes and Their Subsets in Type 1 Diabetes

Abstract

Background. It was assumed that T γδ lymphocytes (T γδ) are involved in the autoimmune destruction of beta cells, presumably as regulatory cells. Objectives. The aim of this paper was to investigate T γδ cells mean percentage (%) in peripheral blood in patients with type 1 diabetes (T1DM) at the time of diagnosis and after twelve months of observation. Material and Methods. A total of 41 patients (21 boys, 51.2%) with new-onset T1DM were included. Exclusion criteria were: Other autoimmune disease, neoplasm, and inflammation. The control group comprised of 14 healthy (7 boys, 50.0%), normostenic children, with normal glucose metabolism and negative history of autoimmune disease and/or diabetes in family. Results. The mean T γδ % in patients with new-onset T1DM (8.03 ± 3.80) and after 12-months of follow-up (6.13 ± 2.15) was lower than in controls (11.23 ± 6.79), p = 0.042 and p = 0.016, respectively. A depletion of those cells after one year was observed (p = 0.067). Gender did not affect the level of T γδ and subsets. No association between T γδ and age neither in T1DM nor controls was observed. Conclusions. Our results support the hypotheses that T γδ play a role in T1DM pathogenesis. If so, the decrease of those lymphocytes makes the probands more vulnerable to autoaggression. We report here for the first time the further depletion of T γδ after one year of insulin treatment, which may be due to the exacerbation of beta cell destruction in the course of insulitis (Adv Clin Exp Med 2016, 25, 4, 665-671).

IL-17 Production from T Helper 17, Mucosal-Associated Invariant T, and γδ Cells in Tuberculosis Infection and Disease

“…γδ T cells comprise 1–5% of peripheral blood lymphocytes ( 13 , 14 ) and occur in a pre-activated differentiation state at high clonal frequencies, allowing for much faster responses compared to other cell types ( 15 ). The invariant γδ TCR recognizes phospho-antigens originating from both the host and bacteria ( 16 ), and evidence of their contribution to the immune response against TB has grown steadily over the years ( 17 ).…”

A Distinctive γδ T Cell Repertoire in NOD Mice Weakens Immune Regulation and Favors Diabetic Disease

“…In humans, several studies have shown that γδ T cells, including V γ 9V δ 2+ γδ T cells [ 78 ] and CD8+ γδ T cells [ 79 , 80 , 81 ], increase prior to disease onset in diabetes-prone individuals, and decrease with disease exacerbation [ 78 , 79 , 80 , 81 , 82 , 83 ]. However, whether such observations indicate that γδ cells protect against the development of diabetes in humans, or instead that their expansion is merely a passive marker brought about by other processes as diabetes develops, is unclear.…”

Skin Resident γδ T Cell Function and Regulation in Wound Repair

“…The underlying molecular and cellular interactions in diabetic nonhealing wounds are important to uncover in order to advance clinical treatments and therapies. Skin γδ T cells are among the cells rendered dysfunctional as mice and humans become obese and develop diabetes [93,114,115,118]. The number, homeostatic turnover, and function of γδ T cells are all negatively impacted, causing defects in barrier function, skin homeostasis, and wound closure [5,93,114,[118][119][120][121].…”

“…Skin γδ T cells are among the cells rendered dysfunctional as mice and humans become obese and develop diabetes [93,114,115,118]. The number, homeostatic turnover, and function of γδ T cells are all negatively impacted, causing defects in barrier function, skin homeostasis, and wound closure [5,93,114,[118][119][120][121]. As hyperglycemia becomes overt in db/db mice, the number of epidermal γδ T cells becomes reduced by half due to reduced homeostatic turnover [93].…”