Open AccessMismatched human leukocyte antigen class II‐restricted CD8 + cytotoxic T cells may mediate selective graft‐versus‐leukemia effects following allogeneic hematopoietic cell transplantation
Author(s) -
Hirosawa Tomoya,
Torikai Hiroki,
Yanagisawa Mayumi,
Kamei Michi,
Imahashi Nobuhiko,
DemachiOkamura Ayako,
Tanimoto Miyoko,
Shiraishi Keiko,
Ito Mamoru,
Miyamura Koichi,
Shibata Kiyosumi,
Kikkawa Fumitaka,
Morishima Yasuo,
Takahashi Toshitada,
Emi Nobuhiko,
Kuzushima Kiyotaka,
Akatsuka Yoshiki
Publication year - 2011
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2011.01949.x
Subject(s) - ctl* , cytotoxic t cell , cd8 , immunology , human leukocyte antigen , antigen , clone (java method) , biology , hematopoietic stem cell transplantation , t cell , context (archaeology) , stem cell , immune system , in vitro , microbiology and biotechnology , dna , biochemistry , genetics , paleontology
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/γc‐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. ( Cancer Sci 2011; 102: 1281–1286)