Faculty Collaboration Database

Memory T cells from minor histocompatibility antigen-vaccinated and virus-immune donors improve GVL and immune reconstitution. Blood 2011 Nov 24;118(22):5965-76

Date

09/16/2011

Pubmed ID

21917752

Pubmed Central ID

PMC3228506

DOI

10.1182/blood-2011-07-367011

Scopus ID

2-s2.0-82155178605 (requires institutional sign-in at Scopus site)   48 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 chronic-phase (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 augmented GVL and protected recipients from LCMV. These data establish a strategy for augmenting GVL and immune reconstitution without elaborate T-cell manipulation.

Author List

Li N, Matte-Martone C, Zheng H, Cui W, Venkatesan S, Tan HS, McNiff J, Demetris AJ, Roopenian D, Kaech S, Shlomchik WD

MESH terms used to index this publication - Major topics in bold

Animals
Cell Proliferation
Graft vs Leukemia Effect
Hematopoiesis
Immunologic Memory
Lymphocytes
Lymphocytic Choriomeningitis
Lymphocytic choriomeningitis virus
Mice
Mice, Inbred C3H
Mice, Inbred C57BL
Mice, Knockout
Minor Histocompatibility Antigens
T-Lymphocytes
Tissue Donors
Transplantation Immunology
Up-Regulation
Vaccination