Lowest numbers of ex vivo selected CD8+ memory T cells can reconstitute pathogen-specific immunity in immuno-compromised hosts.
Patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) are threatened by potentially lethal viral manifestations like Cytomegalovirus (CMV) reactivation. Since the success of todays' 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. MHC-Streptamer-enriched antigen-specific CD62Lhi, but not CD62Llo CD8+ memory T cells proliferated, differentiated and protected against L.m. infections after prophylactic application. Even progenies derived from one single CD62Lhi 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 could be a promising strategy particularly for prophylactic treatment of infectious complications after allo-HSCT.
- Submitted December 31, 2013.
- Accepted April 20, 2014.
- Copyright © 2014 American Society of Hematology