Elevation of activated γδ T cell receptor bearing T lymphocytes in patients with autoimmune chronic liver disease

Abstract

SUMMARYTo study the possible role of T cells bearing the y6 T cell receptor (TCR) heterodimer in the pathogenesis of autoimmune chronic active hepatitis (AI-CAH) and primary sclerosing cholangitis (PSC) in children, we measured levels of 7^+ T cells in the peripheral blood, assessed the proportion of cells bearing the disulphide-linked (BB3+) and non-disulphide-linked (A13+) subtypes of the receptor, and studied the co-expression of TCR-7(5 and the activation markers HLA-DR and IL-2 receptor (IL-2R), and the memory cell marker CD45RO. Percentage levels and absolute numbers of 7^+ T cells were higher in both groups of patients than in controls (f <001), mainly as a result of an increase in both percentage levels and absolute numbers of the A13+ subtype (f <0001). Coexpression of IL-2R and TCR-75 was not found in controls but was present in some patients with AI-CAH (four out of 17) and PSC (six out of 12) at low levels (median 2 3%, range 17-50%). Expression of HLA-DR on 7^+ T cells was similar in both groups of patients and controls. The majority of 7<5+ T cells in children with AI-CAH and PSC also expressed CD45RO (74 7 ± 18 4% and 79-8±24 3%, respectively) at levels significantly higher than in controls (53 3+17 2%, P<QQ\). These results suggest that autoimmune liver diseases in children are associated with an expansion and activation of 7(5+ T cells in the peripheral blood, which may be important in the pathogenesis of these disorders.

Invariant natural killer T cell deficiency leads to the development of spontaneous liver inflammation dependent on γδT cells in mice

“…cdT cells have been reported to play an important effector role in the defense against pathogens, tumors and autoimmune diseases [18]; however, these cells have also been suggested to be involved in the pathogenesis of autoimmunity as effector cells [14,[22][23][24][25]. In the present study, we observed the accumulation of cdT cells in liver tissues from AIH patients, which is consistent with a report that peripheral cdT cells were more numerous in AIH patients compared with control subjects [14].…”

“…Recently, the capacity of cdT cells to produce IL-17, a cytokine that can be involved in autoimmune disorders [19], has been established, and the role of IL-17-producing cdT cells has been evaluated in animal models of autoimmune diseases [20,21]. Moreover, several lines of evidence indicate increased numbers of cdT cells in patients with autoimmune disorders, such as multiple sclerosis [22], Behçet's disease [23], Takayasu arteritis [24], and AIH [14,25], suggesting the involvement of cdT cells in the pathogenesis of autoimmune diseases. However, an association between iNKT cells and cdT cells in the context of autoimmune disorders has not been reported.…”

Transitioning from Idiopathic to Explainable Autoimmune Hepatitis

“…Innate and adaptive systems involved [238] Treg defects implicated but disputed [249,252] Lack of Tregs associated with spontaneous fatal autoimmune hepatitis in mouse model [250] NKT cells have inhibitory and stimulatory actions affected by lipid antigens [257,259] Th1, Th2, Th17 lymphocytes key effectors [238] cd T cells increased in blood and liver [300,301] Identified defects may be correctable by medications, molecular agonists or antagonists, or adoptive cell transfer [238] Recognition of cytopathic mechanisms…”

“…They can also recognize specific antigens presented by class I MHC molecules and secrete the pro-inflammatory cytokines, IL-17 and IFN-c, as part of the adaptive immune response [295,298,299]. Gamma delta (cd) T cells are present in higher concentrations in the peripheral blood [300] and liver tissue [301] of patients with autoimmune hepatitis than in control subjects, and these cells may emerge as indices of disease activity or as additional components of a flawed homeostatic network that cannot adequately modulate the immune response.…”

A new effect of IL-4 on human γδ T cells: promoting regulatory Vδ1 T cells via IL-10 production and inhibiting function of Vδ2 T cells

“…[23][24][25][26][27] IL-4 is a glycosylated, type-I cytokine primarily produced by T cells, natural killer T cells, mast cells and eosinophils. IL-4 initiates signal transduction through either the type I or type II receptor.…”