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
Wh. Zeng et al., 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, BLOOD, 93(9), 1999, pp. 3008-3016
To determine whether the antigen-driven T-cell response is involved in the
pathogenesis of aplastic anemia (AA), we examined the complementarity-deter
mining region 3 (CDR3) size distribution of T-cell receptor (TCR) beta-chai
n (BV) subfamilies in the bone marrow (BM) of untreated AA patients. AA pat
ients who did not respond to immunosuppressive therapy and those who obtain
ed unmaintained remission early after cyclosporine (CyA) or antithymocyte g
lobulin (ATG) therapy exhibited essentially a normal CDR3 size pattern. In
contrast, five patients who needed continuous administration of CyA to main
tain remission exhibited a skewed CDR3 size pattern in a number (>40%) of B
V subfamilies suggestive of clonal predominance. The skewing of CDR3 size d
istribution became less pronounced in one of the CyA-dependent patients whe
n the patient achieved unmaintained remission after a 4-year therapy with C
yA, whereas it persisted longer than 7 years in the other patient requiring
maintenance therapy, Sequencing of BV15 cDNA for which the CDR3 size patte
rn exhibited apparent clonal predominance in all CyA-dependent patients sho
wed high homology of the amino acid sequence of the CDR3 between two differ
ent patients. These findings indicate that antigen-driven expansion of T ce
lls is involved in the pathogenesis of AA characterized by CyA-dependent re
covery of hematopoiesis. (C) 1999 by The American Society of Hematology.