Early lymphocyte recovery after intensive timed sequential chemotherapy for acute myelogenous leukemia: Peripheral oligoclonal expansion of regulatory T cells

Christopher G. Kanakry, Allan D. Hess, Christopher Gocke, Christopher Thoburn, Ferdynand Kos, Christian Meyer, Janet Briel, Leo Luznik, B Douglas Smith, Hyam Levitsky, Judith Karp

Research output: Contribution to journalArticle

Abstract

Few published studies characterize early lymphocyte recovery after intensive chemotherapy for acute myelogenous leukemia (AML). To test the hypothesis that lymphocyte recovery mirrors ontogeny, we characterized early lymphocyte recovery in 20 consecutive patients undergoing induction timed sequential chemotherapy for newly diagnosed AML. Recovering T lymphocytes were predominantly CD4+ and included a greatly expanded population of CD3+CD4+CD25+Foxp3+ T cells. Recovering CD3+CD4+CD25+Foxp3+ T cells were phenotypically activated regulatory T cells and showed suppressive activity on cytokine production in a mixed lymphocyte reaction. Despite an initial burst of thymopoiesis, most recovering regulatory T cells were peripherally derived. Furthermore, regulatory T cells showed marked oligoclonal skewing, suggesting that their peripheral expansion was antigen-driven. Overall, lymphocyte recovery after chemotherapy differs from ontogeny, specifically identifying a peripherally expanded oligoclonal population of activated regulatory T lymphocytes. These differences suggest a stereotyped immunologic recovery shared by patients with newly diagnosed AML after induction timed sequential chemotherapy. Further insight into this oligoclonal regulatory T-cell population will be fundamental toward developing effective immunomodulatory techniques to improve survival for patients with AML.

Original languageEnglish (US)
Pages (from-to)608-617
Number of pages10
JournalBlood
Volume117
Issue number2
DOIs
StatePublished - Jan 13 2011

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Chemotherapy
T-cells
Lymphocytes
Regulatory T-Lymphocytes
Acute Myeloid Leukemia
Drug Therapy
Recovery
T-Lymphocytes
Population
Mixed Lymphocyte Culture Test
Cytokines
Antigens
Survival

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Early lymphocyte recovery after intensive timed sequential chemotherapy for acute myelogenous leukemia : Peripheral oligoclonal expansion of regulatory T cells. / Kanakry, Christopher G.; Hess, Allan D.; Gocke, Christopher; Thoburn, Christopher; Kos, Ferdynand; Meyer, Christian; Briel, Janet; Luznik, Leo; Smith, B Douglas; Levitsky, Hyam; Karp, Judith.

In: Blood, Vol. 117, No. 2, 13.01.2011, p. 608-617.

Research output: Contribution to journalArticle

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