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Prepublished online as a Blood First Edition Paper on July 5, 2002; DOI 10.1182/blood-2002-01-0155.
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Blood, 15 November 2002, Vol. 100, No. 10, pp. 3639-3645
IMMUNOBIOLOGY
Loss of T-lymphocyte clonal dominance in patients with
myelodysplastic syndrome responsive to immunosuppression
James N. Kochenderfer,
Sumiko Kobayashi,
Eric D. Wieder,
Chunliu Su, and
Jeffrey J. Molldrem
From the Section of Transplantation Immunology,
Department of Blood and Marrow Transplantation, University of Texas
M. D. Anderson Cancer Center, Houston.
Evidence suggests that T lymphocyte-mediated inhibition of
hematopoiesis in myelodysplastic syndrome (MDS) contributes to cytopenia in some patients and can be reversed by treatment with immunosuppression. We examined the T-cell repertoires of 12 patients with MDS before and after antithymocyte globulin (ATG)-based
treatment by T-cell receptor V (TCR-V) spectratype analysis. The
average number of TCR-V families with skewed spectratypes,
representative of clonal or oligoclonal T-cell populations, was 7.6 in
MDS patients before treatment and 3.2 in healthy controls
(P = .02). Four patients who recovered effective
hematopoiesis after treatment lost prominent, skewed peaks on their
spectratypes, suggesting loss or diminution of overrepresented clonal
T-cell populations. In contrast, patients who did not recover effective
hematopoiesis showed persistently skewed repertoires 3 to 6 months
after treatment. In 3 patients with skewed repertoires, cDNA from the
complementarity-determining region 3 (CDR3) of 4 TCR-V families was
cloned and repetitively sequenced, confirming clonal T-cell dominance
in each family. In one nonresponder, 16 of 19 CDR3 sequences were
identical, demonstrating that 9.3% of the total T-cell population was
made up of a single clone. By 6 months after treatment, this clone
persisted on both spectratype and DNA sequence complementarity and when
analyzed by flow cytometry was shown to be
CD8+/CD45RA+/HLA-DR . T-cell
clones were not anergic because they could be expanded 4-fold in vitro.
Our results demonstrate that predominant clonal T cells that
appear to be antigen-driven persist in patients with MDS
unresponsive to immunosuppression, but predominant clones regress in
responders to immunosuppression.
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