Details

Autor(en) / Beteiligte

• Hanley, Patrick J
• Melenhorst, Jan J
• Nikiforow, Sarah
• Scheinberg, Phillip
• Blaney, James W
• Demmler-Harrison, Gail
• Cruz, C Russell
• Lam, Sharon
• Krance, Robert A
• Leung, Kathryn S
• Martinez, Caridad A
• Liu, Hao
• Douek, Daniel C
• Heslop, Helen E
• Rooney, Cliona M
• Shpall, Elizabeth J
• Barrett, A John
• Rodgers, John R
• Bollard, Catherine M

Titel

CMV-specific T cells generated from naïve T cells recognize atypical epitopes and may be protective in vivo

Ist Teil von

• Science translational medicine, 2015-04, Vol.7 (285), p.285ra63

Ort / Verlag

United States

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.