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

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, adopti...

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Veröffentlicht in:Blood 2014-07, Vol.124 (4), p.628-637
Hauptverfasser: Stemberger, Christian, Graef, Patricia, Odendahl, Marcus, Albrecht, Julia, Dössinger, Georg, Anderl, Florian, Buchholz, Veit R., Gasteiger, Georg, Schiemann, Matthias, Grigoleit, Götz U., Schuster, Friedhelm R., Borkhardt, Arndt, Versluys, Birgitta, Tonn, Torsten, Seifried, Erhard, Einsele, Hermann, Germeroth, Lothar, Busch, Dirk H., Neuenhahn, Michael
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Sprache:eng
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Zusammenfassung: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 CD62Lhi but not CD62Llo CD8+ memory T cells proliferated, differentiated, and protected against L.m. infections after prophylactic application. Even progenies derived from a single CD62LhiL.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. •Lowest numbers of ex vivo–selected CD8+ memory T cells can reconstitute pathogen-specific immunity in immunocompromised hosts.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2013-12-547349