CMV-specific T cells generated from naïve T cells recognize atypical epitopes and may be protective in vivo
| Autor: | Kathryn S. Leung, Sharon Lam, Helen E. Heslop, Elizabeth J. Shpall, Cliona M. Rooney, Sarah Nikiforow, Hao Liu, Phillip Scheinberg, Caridad Martinez, Catherine M. Bollard, Gail J. Demmler-Harrison, John R. Rodgers, Patrick J. Hanley, J. Joseph Melenhorst, Robert A. Krance, C. Russell Cruz, James W Blaney, Daniel C. Douek, A. John Barrett |
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| Rok vydání: | 2015 |
| Předmět: |
business.industry
T-Lymphocytes T cell Receptors Antigen T-Cell Cytomegalovirus virus diseases CD28 General Medicine Natural killer T cell Virology Article Epitope Epitopes Interleukin 21 medicine.anatomical_structure Immunology medicine Interleukin 12 Humans Cytotoxic T cell Antigen-presenting cell business |
| Zdroj: | Science Translational Medicine. 7 |
| ISSN: | 1946-6242 1946-6234 |
| DOI: | 10.1126/scitranslmed.aaa2546 |
| Popis: | Adoptive transfer of cytomegalovirus (CMV)-specific T cells derived from adult seropositive donors can effectively restore antiviral immunity after transplantation. However, CMV-seronegative donors lack CMV-specific memory T cells, which restricts the availability of virus-specific T cells for immunoprophylaxis. We demonstrate the feasibility of deriving CMV-specific T cells from naïve cells for T cell therapy. Naïve T cells primed to recognize CMV were restricted to different, atypical epitopes than T cells derived from CMV-seropositive individuals; however, these two cell populations had similar avidities. CMV-seropositive individuals also had T cells recognizing these atypical epitopes, but these cells had a lower avidity than those derived from the seronegative subjects, which suggests that high-avidity T cells to these epitopes may be lost over time. Indeed, recipients of cord blood (CB) grafts who did not develop CMV were found by clonotypic analysis to have T cells recognizing atypical CMVpp65 epitopes. Therefore, we examined unmanipulated CB units and found that T cells with T cell receptors restricted by atypical epitopes were the most common, which may explain why these T cells expanded. When infused to recipients, naïve donor-derived virus-specific T cells that recognized atypical epitopes were associated with prolonged periods of CMV-free survival and complete remission. These data suggest that naïve-derived T cells from seronegative patients may be an additional source of cells for CMV immunoprophylaxis. |
| Databáze: | OpenAIRE |
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