Loss of T-lymphocyte clonal dominance in patients with myelodysplastic syndrome responsive to immunosuppression

James N. Kochenderfer, Sumiko Kobayashi, Eric Wieder, Chunliu Su, Jeffrey J. Molldrem

Research output: Contribution to journalArticle

111 Citations (Scopus)

Abstract

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 Vβ (TCR-Vβ) spectratype analysis. The average number of TCR-Vβ 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-Vβ 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 -. 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.

Original languageEnglish
Pages (from-to)3639-3645
Number of pages7
JournalBlood
Volume100
Issue number10
DOIs
StatePublished - Nov 15 2002
Externally publishedYes

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T-cells
Myelodysplastic Syndromes
Immunosuppression
T-Lymphocytes
Hematopoiesis
Clone Cells
T-Cell Antigen Receptor
Complementarity Determining Regions
Therapeutics
Patient treatment
Population
Antilymphocyte Serum
Flow cytometry
DNA sequences
Flow Cytometry
Complementary DNA
Antigens

ASJC Scopus subject areas

  • Hematology

Cite this

Loss of T-lymphocyte clonal dominance in patients with myelodysplastic syndrome responsive to immunosuppression. / Kochenderfer, James N.; Kobayashi, Sumiko; Wieder, Eric; Su, Chunliu; Molldrem, Jeffrey J.

In: Blood, Vol. 100, No. 10, 15.11.2002, p. 3639-3645.

Research output: Contribution to journalArticle

Kochenderfer, James N. ; Kobayashi, Sumiko ; Wieder, Eric ; Su, Chunliu ; Molldrem, Jeffrey J. / Loss of T-lymphocyte clonal dominance in patients with myelodysplastic syndrome responsive to immunosuppression. In: Blood. 2002 ; Vol. 100, No. 10. pp. 3639-3645.
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