Chronic myelogenous leukemia shapes host immunity by selective deletion of high-avidity leukemia-specific T cells

Jeffrey J. Molldrem, Peter P. Lee, Shreya Kant, Eric Wieder, Weidong Jiang, Sijie Lu, Changqing Wang, Mark M. Davis

Research output: Contribution to journalArticle

173 Citations (Scopus)

Abstract

We have shown that cytotoxic T lymphocytes specific for PR1, an HLA-A2-restricted nonopeptide derived from proteinase 3, kill leukemia cells and may contribute to the elimination of chronic myelogenous leukemia (CML) after treatment with IFN or allogeneic bone marrow transplant. Some patients with persistent disease also have circulating PR1-specific T cells, however, suggesting the likelihood of immune tolerance. Here we show that both high- and low-avidity PR1-specific T cells from the peripheral blood of healthy donors can be identified and selectively expanded in vitro. Although high-avidity PR1-specific T cells killed CML more effectively than low-avidity T cells, only high-avidity T cells underwent apoptosis when stimulated with high PR1 peptide concentration or when exposed to leukemia that overexpressed proteinase 3. No high-avidity PR1-specific T cells could be identified or expanded from newly diagnosed leukemia patients, whereas low-avidity T cells were readily expanded. Circulating high-avidity PR1-specific T cells were identified in IFN-sensitive patients in cytogenetic remission, however. These results provide evidence that CML shapes the host immune response and that leukemia outgrowth may result in part from leukemia-induced selective deletion of high-avidity PR1-specific T cells.

Original languageEnglish
Pages (from-to)639-647
Number of pages9
JournalJournal of Clinical Investigation
Volume111
Issue number5
DOIs
StatePublished - Mar 1 2003
Externally publishedYes

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T-Cell Leukemia
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Immunity
T-Lymphocytes
Leukemia
Myeloblastin
HLA-A2 Antigen
Immune Tolerance
Cytotoxic T-Lymphocytes
Blood Donors
Cytogenetics
Bone Marrow
Apoptosis
Transplants
Peptides

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Chronic myelogenous leukemia shapes host immunity by selective deletion of high-avidity leukemia-specific T cells. / Molldrem, Jeffrey J.; Lee, Peter P.; Kant, Shreya; Wieder, Eric; Jiang, Weidong; Lu, Sijie; Wang, Changqing; Davis, Mark M.

In: Journal of Clinical Investigation, Vol. 111, No. 5, 01.03.2003, p. 639-647.

Research output: Contribution to journalArticle

Molldrem, Jeffrey J. ; Lee, Peter P. ; Kant, Shreya ; Wieder, Eric ; Jiang, Weidong ; Lu, Sijie ; Wang, Changqing ; Davis, Mark M. / Chronic myelogenous leukemia shapes host immunity by selective deletion of high-avidity leukemia-specific T cells. In: Journal of Clinical Investigation. 2003 ; Vol. 111, No. 5. pp. 639-647.
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