Lowest numbers of primary CD8(+) T cells can reconstitute protective immunity upon adoptive immunotherapy

Blood. 2014 Jul 24;124(4):628-37. doi: 10.1182/blood-2013-12-547349. Epub 2014 May 22.


Patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) are threatened by potentially lethal viral manifestations like cytomegalovirus (CMV) reactivation. Because the success of today's virostatic treatment is limited by side effects and resistance development, adoptive transfer of virus-specific memory T cells derived from the stem cell donor has been proposed as an alternative therapeutic strategy. In this context, dose minimization of adoptively transferred T cells might be warranted for the avoidance of graft-versus-host disease (GVHD), in particular in prophylactic settings after T-cell-depleting allo-HSCT protocols. To establish a lower limit for successful adoptive T-cell therapy, we conducted low-dose CD8(+) T-cell transfers in the well-established murine Listeria monocytogenes (L.m.) infection model. Major histocompatibility complex-Streptamer-enriched antigen-specific CD62L(hi) but not CD62L(lo) CD8(+) memory T cells proliferated, differentiated, and protected against L.m. infections after prophylactic application. Even progenies derived from a single CD62L(hi) L.m.-specific CD8(+) T cell could be protective against bacterial challenge. In analogy, low-dose transfers of Streptamer-enriched human CMV-specific CD8(+) T cells into allo-HSCT recipients led to strong pathogen-specific T-cell expansion in a compassionate-use setting. In summary, low-dose adoptive T-cell transfer (ACT) could be a promising strategy, particularly for prophylactic treatment of infectious complications after allo-HSCT.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Differentiation
  • Cell Proliferation
  • Child
  • Cytomegalovirus / isolation & purification
  • Cytomegalovirus Infections / immunology*
  • Cytomegalovirus Infections / metabolism
  • Cytomegalovirus Infections / therapy
  • Graft vs Host Disease / immunology*
  • Graft vs Host Disease / metabolism
  • Graft vs Host Disease / therapy
  • Hematopoietic Stem Cell Transplantation
  • Homeodomain Proteins / physiology
  • Humans
  • Immunization
  • Immunotherapy, Adoptive*
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Ovalbumin / physiology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / immunology*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / metabolism
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy
  • Severe Combined Immunodeficiency / immunology*
  • Severe Combined Immunodeficiency / metabolism
  • Severe Combined Immunodeficiency / therapy
  • Transplantation, Homologous
  • Virus Activation


  • Homeodomain Proteins
  • RAG-1 protein
  • Ovalbumin