Memory T cells from minor histocompatibility antigen-vaccinated and virus-immune donors improve GVLand immune reconstitution

Ning Li, Catherine Matte-Martone, Hong Zheng, Weiguo Cui, Srividhya Venkatesan, Hung Sheng Tan, Jennifer McNiff, Anthony J. Demetris, Derry Roopenian, Susan Kaech, Warren D. Shlomchik

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Donor T cells contribute to the success of allogeneic hematopoietic stem cell transplantation (alloSCT). Alloreactive donor T cells attack leukemia cells, mediating the GVL effect. Donor T cells, including the memory T cells (T M) that are generated after infection, also promote immune reconstitution. Nonetheless, leukemia relapse and infection are major sources of treatment failure. Efforts to augment GVL and immune reconstitution have been limited by GVHD, the attack by donor T cells on host tissues. One approach to augmenting GVL has been to infuse ex vivo-generated T cells with defined specificities; however, this requires expertise that is not widely available. In the present study, we tested an alternative approach, adoptive immunotherapy with CD8 + T M from donors vaccinated against a single minor histocompatibility antigen (miHA) expressed by leukemia cells. Vaccination against the miHA H60 greatly augmented T M-mediated GVL against mouse chronicphase (CP-CML) and blast crisis chronic myeloid leukemia (BC-CML). T M-mediated GVL was antigen specific and was optimal when H60 expression was hematopoietically restricted. Even when H60 was ubiquitous, donor H60 vaccination had a minimal impact on GVHD. T M from lymphocytic choriomeningitis virus (LCMV)-immune and H60-vaccinated donors augmentedGVLand protected recipients from LCMV. These data establish a strategy for augmentingGVLand immune reconstitution without elaborate T-cell manipulation.

Original languageEnglish (US)
Pages (from-to)5965-5976
Number of pages12
JournalBlood
Volume118
Issue number22
DOIs
StatePublished - Nov 24 2011

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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