PMID- 21466613 OWN - NLM STAT- MEDLINE DCOM- 20110826 LR - 20111117 IS - 1349-7006 (Electronic) IS - 1347-9032 (Linking) VI - 102 IP - 7 DP - 2011 Jul TI - Mismatched human leukocyte antigen class II-restricted CD8(+) cytotoxic T cells may mediate selective graft-versus-leukemia effects following allogeneic hematopoietic cell transplantation. PG - 1281-6 LID - 10.1111/j.1349-7006.2011.01949.x [doi] AB - Partial human leukocyte antigen (HLA)-mismatched hematopoietic stem cell transplantation (HSCT) is often performed when an HLA-matched donor is not available. In these cases, CD8(+) or CD4(+) T cell responses are induced depending on the mismatched HLA class I or II allele(s). Herein, we report on an HLA-DRB1*08:03-restricted CD8(+) CTL clone, named CTL-1H8, isolated from a patient following an HLA-DR-mismatched HSCT from his brother. Lysis of a patient Epstein-Barr virus-transformed B cell line (B-LCL) by CTL-1H8 was inhibited after the addition of blocking antibodies against HLA-DR and CD8, whereas antibodies against pan-HLA class I or CD4 had no effect. The 1H8-CTL clone did not lyse the recipient dermal fibroblasts whose HLA-DRB1*08:03 expression was upregulated after 1 week cytokine treatment. Engraftment of HLA-DRB1*08:03-positive primary leukemic stem cells in non-obese diabetic/severe combined immunodeficient/gammac-null (NOG) mice was completely inhibited by the in vitro preincubation of cells with CTL-1H8, suggesting that HLA-DRB1*08:03 is expressed on leukemic stem cells. Finally, analysis of the precursor frequency of CD8(+) CTL specific for recipient antigens in post-HSCT peripheral blood T cells revealed a significant fraction of the total donor CTL responses towards the individual mismatched HLA-DR antigen in two patients. These findings underscore unexpectedly significant CD8 T cell responses in the context of HLA class II. CI - (c) 2011 Japanese Cancer Association. FAU - Hirosawa, Tomoya AU - Hirosawa T AD - Division of Immunology, Aichi Cancer Center Research Institute, Nagoya, Japan. FAU - Torikai, Hiroki AU - Torikai H FAU - Yanagisawa, Mayumi AU - Yanagisawa M FAU - Kamei, Michi AU - Kamei M FAU - Imahashi, Nobuhiko AU - Imahashi N FAU - Demachi-Okamura, Ayako AU - Demachi-Okamura A FAU - Tanimoto, Miyoko AU - Tanimoto M FAU - Shiraishi, Keiko AU - Shiraishi K FAU - Ito, Mamoru AU - Ito M FAU - Miyamura, Koichi AU - Miyamura K FAU - Shibata, Kiyosumi AU - Shibata K FAU - Kikkawa, Fumitaka AU - Kikkawa F FAU - Morishima, Yasuo AU - Morishima Y FAU - Takahashi, Toshitada AU - Takahashi T FAU - Emi, Nobuhiko AU - Emi N FAU - Kuzushima, Kiyotaka AU - Kuzushima K FAU - Akatsuka, Yoshiki AU - Akatsuka Y LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110509 PL - England TA - Cancer Sci JT - Cancer science JID - 101168776 RN - 0 (HLA-D Antigens) RN - 0 (HLA-DR Antigens) RN - 0 (HLA-DR Serological Subtypes) RN - 0 (HLA-DR8 antigen) RN - 0 (HLA-DRB1 Chains) SB - IM MH - Animals MH - CD8-Positive T-Lymphocytes/*immunology MH - Graft vs Host Disease/etiology MH - Graft vs Leukemia Effect/*immunology MH - HLA-D Antigens/*immunology MH - HLA-DR Antigens/immunology MH - HLA-DR Serological Subtypes MH - HLA-DRB1 Chains MH - Hematopoietic Stem Cell Transplantation/*adverse effects MH - *Histocompatibility Testing MH - Humans MH - Male MH - Mice MH - Precursor Cell Lymphoblastic Leukemia-Lymphoma/immunology/surgery MH - Transplantation, Homologous EDAT- 2011/04/07 06:00 MHDA- 2011/08/30 06:00 CRDT- 2011/04/07 06:00 PHST- 2011/04/07 06:00 [entrez] PHST- 2011/04/07 06:00 [pubmed] PHST- 2011/08/30 06:00 [medline] AID - 10.1111/j.1349-7006.2011.01949.x [doi] PST - ppublish SO - Cancer Sci. 2011 Jul;102(7):1281-6. doi: 10.1111/j.1349-7006.2011.01949.x. Epub 2011 May 9.