Differential expression of THELPER1 cytokines upon antigen stimulation predicts ex vivo proliferative potential and cytokine production of virus‐specific T cells following re‐stimulation. Issue 5 (9th September 2014)

• Record Type: Journal Article
• Authors: Feucht, J.; Leibold, J.; Halder, A.; Kayser, S.; Hartl, L.; Rammensee, H.‐G.; Handgretinger, R.; Feuchtinger, T.
• Is Part Of: Transplant infectious disease. Volume 16:Issue 5(2014)
• Page Start: 713
• Page End: 723
• Publication Date: 2014-09-09
• Subjects: Transplantation of organs, tissues, etc -- Complications -- Periodicals; Communicable diseases -- Periodicals; Infection -- Periodicals; 617.01
• DOI: 10.1111/tid.12281
• Languages: English
• ISSNs: 1398-2273

Abstract

<abstract abstract-type="main" id="tid12281-abs-0001"> <title>Abstract</title> <sec id="tid12281-sec-0001" sec-type="section"> <title>Introduction</title> <p>Cytomegalovirus (CMV) and human adenovirus (ADV) infections are causes of morbidity after stem cell transplantation. Antigen (Ag)‐specific T cells are essential for the control of viral infections. However, <italic>in vivo</italic> expansion potential of T‐cell subpopulations is hardly predictable in humans. Furthermore, <italic>ex vivo</italic> identification of human T cells with repopulating capacity for adoptive T‐cell transfer has been difficult.</p> </sec> <sec id="tid12281-sec-0002" sec-type="section"> <title>Methods</title> <p>We analyzed Ag‐specific T‐cell populations, subdivided according to the expression of different T<sub>HELPER‐</sub>1 (Th1) cytokines. Isolation by flow cytometry was based on interferon‐gamma (IFN)‐γ, interleukin (IL)‐2, or tumor necrosis factor‐alpha (TNF‐α) secretion of T cells after <italic>ex vivo</italic> stimulation with the Ags hexon (for ADV) and pp65 (for CMV). Isolated T cells were expanded and examined for functional characteristics, expansion/differentiation potential, and naïve, effector memory, central memory, and late effector phenotypes.</p> </sec> <sec id="tid12281-sec-0003" sec-type="section"> <title>Results</title> <p>Isolation based on IFN‐γ production provides a T‐cell population with a mixture of early, central memory, and effector memory T cells, high expansion potential, and effective cytokine production. Selection of T cells with Ag‐specific expression of IL‐2 or TNF‐α, however, results in a T‐cell population with reduced proliferation and lower effector potential after expansion.</p> </sec> <sec id="tid12281-sec-0004" sec-type="section"> <title>Conclusion</title> <p>We conclude that the exclusive secretion of IFN‐γ in the human antiviral T‐cell responses preferentially leads to higher repopulation capacities of antiviral T cells, compared to IL‐2 or TNF‐α secreting T‐cell populations.</p> </sec> </abstract>