Analysis of T-cell repertoire in hepatitis-associated aplastic anemia.
Hepatitis-associated aplastic anemia (HAA) is a syndrome of bone marrow failure following an acute attack of seronegative hepatitis. Clinical features and liver histology suggest a central role for an immune-mediated mechanism. To characterize the immune response, we investigated the T-cell repertoire (T-cell receptor [TCR] V(beta) chain subfamily) of intrahepatic lymphocytes in HAA patients by TCR spectratyping. In 6 of 7 HAA liver samples, a broad skewing pattern in the 21 V(beta) subfamilies tested was observed. In total, 62% +/- 18% of HAA spectratypes showed a skewed pattern, similar to 68% +/- 18% skewed spectratype patterns in 3 of 4 patients with confirmed viral hepatitis. Additionally, the T-cell repertoire had similarly low levels of complexity. In the peripheral blood lymphocytes (PBLs) of a separate group of HAA patients prior to treatment, 60% +/- 15% skewed spectratypes were detected, compared with only 18% +/- 8% skewed spectratypes in healthy controls. After successful immunosuppressive treatment, an apparent reversion to a normal T-cell repertoire with a corresponding significant increase in T-cell repertoire complexity was observed in the HAA samples. In conclusion, our data suggest an antigen-driven T-cell expansion in HAA and achievement of a normal T-cell repertoire during recovery from HAA.
Lu
Jun
J
Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bldg 10, 9000 Rockville Pike, Bethesda, MD 20892-1652, USA.
Basu
Atanu
A
Melenhorst
J Joseph
JJ
Young
Neal S
NS
Brown
Kevin E
KE
D000741:Anemia, Aplastic / Q000150:complications* / Q000276:immunology*; D001853:Bone Marrow / Q000473:pathology; D005434:Flow Cytometry; D006505:Hepatitis / Q000209:etiology* / Q000276:immunology; D006801:Humans; D008099:Liver / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D011948:Receptors, Antigen, T-Cell