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Isolation of a T-cell clone showing HLA-DRB1*0405-restricted cytotoxicity
for hematopoietic cells in a patient with aplastic anemia
S Nakao, A Takami, H Takamatsu, W Zeng, N Sugimori, H Yamazaki, Y Miura, M Ueda, S Shiobara, T Yoshioka, T Kaneshige, M Yasukawa and T Matsuda
Third Department of Medicine, Kanazawa University School of Medicine,
Ishikawa, Japan.
The existence of T cells capable of inhibiting in vitro hematopoiesis has
been shown in aplastic anemia (AA), although whether such inhibition is
mediated by a specific immune reaction involving an HLA allele remained
unknown. We isolated a CD4+ Vbeta21+ T-cell clone that was most dominant
among Vbeta21+ T cells in the bone marrow (BM) of an AA patient whose
HLA-DRB1 alleles included 1501 and 0405. The T-cell clone named NT4.2 lysed
an autologous Epstein-Barr virus-transformed lymphoblastoid cell line (LCL)
and phytohemagglutinin-stimulated lymphocytes (PHA-blasts) as well as
allogeneic LCLs sharing HLA- DRB1*0405. Cytotoxicity against LCL cells and
PHA-blasts by NT4.2 was blocked by anti-HLA-DR monoclonal antibody (MoAb)
or anti-CD3 MoAb. NT4.2 also lysed autologous BM mononuclear cells enriched
with CD34+ cells that had been cultured for one week in the presence of
colony- stimulating factors as well as allogeneic CD34+ cells of a normal
individual carrying HLA-DRB1*0405, cultured in the same way. Moreover,
NT4.2 strongly inhibited colony formation by hematopoietic progenitor cells
derived from cultured CD34+ cells sharing HLA-DRB1*0405. These results
indicate that the AA patient has T cells capable of killing hematopoietic
cells in an HLA-DRB1*0405-restricted manner and that such cytotoxic T cells
may contribute to the pathogenesis of AA.
Volume 89,
Issue 10,
pp. 3691-3699,
05/15/1997
Copyright © 1997 by The American Society of Hematology
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