Differential expression of T(HELPER)1 cytokines upon antigen stimulation predicts ex vivo proliferative potential and cytokine production of virus-specific T cells following re-stimulation
TRANSPLANT INFECTIOUS DISEASE
Authors: Feucht, J.; Leibold, J.; Halder, A.; Kayser, S.; Hartl, L.; Rammensee, H. -G.; Handgretinger, R.; Feuchtinger, T.
Abstract
IntroductionCytomegalovirus (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, in vivo expansion potential of T-cell subpopulations is hardly predictable in humans. Furthermore, ex vivo identification of human T cells with repopulating capacity for adoptive T-cell transfer has been difficult. MethodsWe analyzed Ag-specific T-cell populations, subdivided according to the expression of different T(HELPER-)1 (Th1) cytokines. Isolation by flow cytometry was based on interferon-gamma (IFN)-, interleukin (IL)-2, or tumor necrosis factor-alpha (TNF-) secretion of T cells after ex vivo 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 naive, effector memory, central memory, and late effector phenotypes. ResultsIsolation based on IFN- 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-, however, results in a T-cell population with reduced proliferation and lower effector potential after expansion. ConclusionWe conclude that the exclusive secretion of IFN- in the human antiviral T-cell responses preferentially leads to higher repopulation capacities of antiviral T cells, compared to IL-2 or TNF- secreting T-cell populations.
Associations of Adenovirus Genotypes in Korean Acute Gastroenteritis Patients with Respiratory Symptoms and Intussusception
BIOMED RESEARCH INTERNATIONAL
Authors: Kim, Jae-Seok; Lee, Su Kyung; Ko, Dae-Hyun; Hyun, Jungwon; Kim, Han-Sung; Song, Wonkeun; Kim, Hyun Soo
Abstract
Human adenoviruses (HAdVs) cause a wide range of diseases, including respiratory infections and gastroenteritis, and have more than 65 genotypes. To investigate the current genotypes of circulating HAdV strains, we performed molecular genotyping of HAdVs in the stool from patients with acute gastroenteritis and tried to determine their associations with clinical symptoms. From June 2014 to May 2016, 3,901 fecal samples were tested for an AdV antigen, and 254 samples (6.5%) yielded positive results. Genotyping using PCR and sequencing of the capsid hexon gene was performed for 236 AdV antigen-positive fecal specimens. HAdV-41, of species F, was the most prevalent genotype (60.6%), followed by HAdV-2 of species C (13.8%). Other genotypes, including HAdV3, HAdV-1, HAdV-5, HAdV-6, HAdV-31, HAdV-40, HAdV-12, and HAdV-55, were also detected. Overall, 119 patients (50.4%) showed concomitant respiratory symptoms, and 32 patients (13.6%) were diagnosed with intussusception. HAdV-1 and HAdV-31 were significantly associated with intussusception (p < 0.05). Our results demonstrate the recent changes in trends of circulating AdV genotypes associated with gastroenteritis in Korea, which should be of value for improving the diagnosis and developing new detection, treatment, and prevention strategies for broad application in clinical laboratories.