Elevation of activated gamma delta T cell receptor bearing T lymphocytes in patients with autoimmune chronic liver disease.
To study the possible role of T cells bearing the gamma delta 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 gamma delta+ 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-gamma delta and the activation markers HLA-DR and IL-2 receptor (IL-2R), and the memory cell marker CD45RO. Percentage levels and absolute numbers of gamma delta +T cells were higher in both groups of patients than in controls (P less than 0.01), mainly as a result of an increase in both percentage levels and absolute numbers of the A13+ subtype (P less than 0.001). Co-expression of IL-2R and TCR-gamma delta 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 1.7-5.0%). Expression of HLA-DR on gamma delta+ T cells was similar in both groups of patients and controls. The majority of gamma delta+ 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 less than 0.01). These results suggest that autoimmune liver diseases in children are associated with an expansion and activation of gamma delta+ T cells in the peripheral blood, which may be important in the pathogenesis of these disorders.
Wen
L
L
Department of Immunology, King's College School of Medicine and Dentistry, London, UK.
Peakman
M
M
Mieli-Vergani
G
G
Vergani
D
D
D000293:Adolescent; D015703:Antigens, CD / Q000096:biosynthesis; D001327:Autoimmune Diseases / Q000276:immunology*; D002648:Child; D015209:Cholangitis, Sclerosing / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006521:Hepatitis, Chronic / Q000276:immunology; D006649:Histocompatibility Antigens / Q000096:biosynthesis; D006801:Humans; D017493:Leukocyte Common Antigens; D008107:Liver Diseases / Q000276:immunology*; D008297:Male; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000096:biosynthesis*; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000378:metabolism*
D015703:Antigens, CD; D006684:HLA-DR Antigens; D006649:Histocompatibility Antigens; D016692:Receptors, Antigen, T-Cell, gamma-delta; D015375:Receptors, Interleukin-2; D017493:Leukocyte Common Antigens