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Blood, Vol. 93 No. 9 (May 1), 1999:
pp. 3008-3016
Characterization of T-Cell Repertoire of the Bone Marrow in
Immune-Mediated Aplastic Anemia: Evidence for the Involvement of
Antigen-Driven T-Cell Response in Cyclosporine-Dependent Aplastic
Anemia
Weihua Zeng,
Shinji Nakao,
Hideyuki Takamatsu,
Akihiro Yachie,
Akiyoshi Takami,
Yukio Kondo,
Naomi Sugimori,
Hirohito Yamazaki,
Yuji Miura,
Shintaro Shiobara, and
Tamotsu Matsuda
From the Third Department of Medicine, the Department of Pediatrics,
and Blood Transfusion Section, Kanazawa University School of Medicine,
Kanazawa, Japan.
To determine whether the antigen-driven T-cell response is involved
in the pathogenesis of aplastic anemia (AA), we examined the
complementarity-determining region 3 (CDR3) size distribution of T-cell
receptor (TCR)  -chain (BV) subfamilies in the bone marrow (BM) of
untreated AA patients. AA patients who did not respond to
immunosuppressive therapy and those who obtained unmaintained remission
early after cyclosporine (CyA) or antithymocyte globulin (ATG) therapy
exhibited essentially a normal CDR3 size pattern. In contrast, five
patients who needed continuous administration of CyA to maintain
remission exhibited a skewed CDR3 size pattern in a number (>40%) of
BV subfamilies suggestive of clonal predominance. The skewing of CDR3
size distribution became less pronounced in one of the CyA-dependent
patients when the patient achieved unmaintained remission after a
4-year therapy with CyA, whereas it persisted longer than 7 years in
the other patient requiring maintenance therapy. Sequencing of BV15
cDNA for which the CDR3 size pattern exhibited apparent clonal
predominance in all CyA-dependent patients showed high homology of the
amino acid sequence of the CDR3 between two different patients. These
findings indicate that antigen-driven expansion of T cells is involved
in the pathogenesis of AA characterized by CyA-dependent recovery of hematopoiesis.
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