Limited heterogeneity of T cell receptor BV usage in aplastic anemia
Weihua Zeng, … , Guibin Chen, Neal S. Young
Weihua Zeng, … , Guibin Chen, Neal S. Young
Published September 1, 2001
Citation Information: J Clin Invest. 2001;108(5):765-773. https://doi.org/10.1172/JCI12687.
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Article

Limited heterogeneity of T cell receptor BV usage in aplastic anemia

Abstract

Immune mediation of aplastic anemia (AA) has been inferred from clinical responsiveness to immunosuppressive therapies and a large body of circumstantial laboratory evidence. However, neither the immune response nor the nature of the antigens recognized has been well characterized. We established a large number of CD4 and CD8 T cell clones from a patient with AA and analyzed their T cell receptor (TCR) usage. Most CD4 clones displayed BV5, whereas most CD8 clones displayed BV13. We found sequence identity for complementarity determining region 3 (CDR3) among a majority of CD4 clones; the same sequence was present in marrow lymphocytes from four other patients with AA but was not detected in controls. The dominant CD4 clone showed a Th1 secretion pattern, lysed autologous CD34 cells, and inhibited their hematopoietic colony formation. In three of four patients, successful immunosuppressive treatment led to marked decrease in clones bearing the dominant CDR3 BV5 sequence. These results suggest surprisingly limited heterogeneity of the T cell repertoire in an individual patient and similarity at the molecular level of the likely pathological lymphocyte response among multiple patients with AA, consistent with recognition of limited numbers of antigens shared by individuals with the same HLA type in this disease.

Authors

Weihua Zeng, Jaroslaw P. Maciejewski, Guibin Chen, Neal S. Young

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Functional analysis of JZ1.1. (a) Cytotoxicity for autologous CD34 cells...
Functional analysis of JZ1.1. (a) Cytotoxicity for autologous CD34 cells, normal CD34+ cells (N1, HLA-matched for DR2; N2, DR-mismatched). CD34 cells were labeled with calcein-AM and incubated with differing numbers of JZ1.1 cells in a 4-hour cytotoxicity assay. (b) Blocking of cytotoxicity. Autologous CD34+ cells were incubated with JZ1.1 cells in medium alone or with addition of 10 μg/ml of the indicated mAb’s. Mean percentage of specific lysis was determined from triplicate cultures after 4 hours of incubation. (c) Effect of JZ1.1 on autologous hematopoietic progenitor cell growth. Ten thousand freshly isolated CD34 cells were incubated in medium alone or with 1 × 105 JZ1.1 cells for 16 hours and then mixed with methylcellulose medium containing hematopoietic growth factors; colonies were enumerated after 2–3 weeks of culture. Data are expressed as mean ± SD of replicate plates.