{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T06:31:24Z","timestamp":1782801084484,"version":"3.54.5"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2015,10,1]],"date-time":"2015-10-01T00:00:00Z","timestamp":1443657600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>BCR-ABL+ acute lymphoblastic leukemia patients have transient responses to current therapies. However, the fusion of BCR to ABL generates a potential leukemia-specific Ag that could be a target for immunotherapy. We demonstrate that the immune system can limit BCR-ABL+ leukemia progression although ultimately this immune response fails. To address how BCR-ABL+ leukemia escapes immune surveillance, we developed a peptide: MHC class II tetramer that labels endogenous BCR-ABL\u2013specific CD4+ T cells. Naive mice harbored a small population of BCR-ABL\u2013specific T cells that proliferated modestly upon immunization. The small number of naive BCR-ABL\u2013specific T cells was due to negative selection in the thymus, which depleted BCR-ABL\u2013specific T cells. Consistent with this observation, we saw that BCR-ABL\u2013specific T cells were cross-reactive with an endogenous peptide derived from ABL. Despite this cross-reactivity, the remaining population of BCR-ABL reactive T cells proliferated upon immunization with the BCR-ABL fusion peptide and adjuvant. In response to BCR-ABL+ leukemia, BCR-ABL\u2013specific T cells proliferated and converted into regulatory T (Treg) cells, a process that was dependent on cross-reactivity with self-antigen, TGF-\u03b21, and MHC class II Ag presentation by leukemic cells. Treg cells were critical for leukemia progression in C57BL\/6 mice, as transient Treg cell ablation led to extended survival of leukemic mice. Thus, BCR-ABL+ leukemia actively suppresses antileukemia immune responses by converting cross-reactive leukemia-specific T cells into Treg cells.<\/jats:p>","DOI":"10.4049\/jimmunol.1501291","type":"journal-article","created":{"date-parts":[[2015,9,17]],"date-time":"2015-09-17T03:28:43Z","timestamp":1442460523000},"page":"4028-4037","source":"Crossref","is-referenced-by-count":29,"title":["Adaptive Immunity to Leukemia Is Inhibited by Cross-Reactive Induced Regulatory T Cells"],"prefix":"10.1093","volume":"195","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4781-7707","authenticated-orcid":false,"given":"Luke S","family":"Manlove","sequence":"first","affiliation":[{"name":"Center for Immunology, University of Minnesota , Minneapolis, MN 55455"},{"name":"Department of Laboratory Medicine and Pathology, University of Minnesota , Minneapolis, MN 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine E","family":"Berquam-Vrieze","sequence":"additional","affiliation":[{"name":"Center for Immunology, University of Minnesota , Minneapolis, MN 55455"},{"name":"Department of Laboratory Medicine and Pathology, University of Minnesota , Minneapolis, MN 55455"},{"name":"Masonic Cancer Center, University of Minnesota , Minneapolis, MN 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen E","family":"Pauken","sequence":"additional","affiliation":[{"name":"Center for Immunology, University of Minnesota , Minneapolis, MN 55455"},{"name":"Institute for Immunology, Department of Microbiology, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA 19444"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard T","family":"Williams","sequence":"additional","affiliation":[{"name":"Puma Biotechnology, Inc. , Los Angeles, CA 90024"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8009-7655","authenticated-orcid":false,"given":"Marc K","family":"Jenkins","sequence":"additional","affiliation":[{"name":"Center for Immunology, University of Minnesota , Minneapolis, MN 55455"},{"name":"Department of Microbiology, University of Minnesota , Minneapolis, MN 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A","family":"Farrar","sequence":"additional","affiliation":[{"name":"Center for Immunology, University of Minnesota , Minneapolis, MN 55455"},{"name":"Department of Laboratory Medicine and Pathology, University of Minnesota , Minneapolis, MN 55455"},{"name":"Masonic Cancer Center, University of Minnesota , Minneapolis, MN 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,10,15]]},"reference":[{"key":"2025030704181168000_r1","doi-asserted-by":"crossref","first-page":"2189","DOI":"10.1056\/NEJMoa1406498","article-title":"Genetic basis for clinical response to CTLA-4 blockade in melanoma","volume":"371","author":"Snyder","year":"2014","journal-title":"N. 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