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Article

ThymicPeptides Reverse Immune Exhaustion in Patients with Reactivated Human Alphaherpesvirus1 Infections

1
Department of Otolaryngology and Laryngeal Oncology, Medical University of Lublin, 20-954 Lublin, Poland
2
Department of Clinical Immunology and Immunotherapy, Medical University of Lublin, 20-093 Lublin, Poland
3
Department of Immunology, St. John’s Cancer Centre, Lublin 20-090, Poland
4
Department of Pediatric Endocrinology and Diabetology, Medical University, 20-093 Lublin, Poland
5
Department of Pharmaceutical Microbiology, Medical University, 20-093 Lublin, Poland
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(7), 2379; https://doi.org/10.3390/ijms21072379
Received: 22 February 2020 / Revised: 11 March 2020 / Accepted: 29 March 2020 / Published: 30 March 2020
(This article belongs to the Special Issue Natural Products against Viral Infections II)
Recurrent infection with human alphaherpesvirus 1 (HHV-1) may be associated with immune exhaustion that impairs virus elimination. Thymic peptides enhance immune function and thus could overcome immune exhaustion. In this study, we investigated whether reactivation of herpes infections was associated with immune exhaustion. Moreover, we examined the impact of treatment with thymostimulin on the expression of programmed cell death protein 1 (PD-1) and its ligand (PD-L1) on T and B lymphocytes in patients suffering from recurrent HHV-1 reactivation. We also assessed the effector function of peripheral blood mononuclear cells (PBMCs) after stimulation with thymic peptides. We enrolled 50 women with reactivated HHV-1 infections and healthy volunteers. We measured the expression of various activation and exhaustion markers on the surface of PBMCs using flow cytometry. In ex vivo experiments, we measured the secretion of inflammatory cytokines by PBMCs cultured with thymostimulin. Compared with controls, patients with reactivated HHV-1 infections had increased percentages of CD3+ co-expressing CD25, an activation marker (p < 0.001). Moreover, these patients had increased percentages of CD4+ and CD8+ cells co-expressing the inhibitory markers PD-1 and PD-L1. In cultures of PBMCs from the patients, thymostimulin increased the secretion of interferon gamma (p < 0.001) and interleukin (IL)-2 (p = 0.023), but not IL-4 or IL-10.Two-month thymostimulin therapy resulted in no reactivation of HHV-1 infection during this period and the reduction of PD-1 and PD-L1 expression on the surface of T and B lymphocytes (p < 0.001). In conclusion, reactivation of herpes infection is associated with immune exhaustion, which could be reversed by treatment with thymic peptides. View Full-Text
Keywords: herpes simplex; immune exhaustion; programmed cell death protein 1; thymic peptides herpes simplex; immune exhaustion; programmed cell death protein 1; thymic peptides
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MDPI and ACS Style

Hymos, A.; Grywalska, E.; Klatka, J.; Klatka, M.; Korona-Głowniak, I.; Roliński, J. ThymicPeptides Reverse Immune Exhaustion in Patients with Reactivated Human Alphaherpesvirus1 Infections. Int. J. Mol. Sci. 2020, 21, 2379. https://doi.org/10.3390/ijms21072379

AMA Style

Hymos A, Grywalska E, Klatka J, Klatka M, Korona-Głowniak I, Roliński J. ThymicPeptides Reverse Immune Exhaustion in Patients with Reactivated Human Alphaherpesvirus1 Infections. International Journal of Molecular Sciences. 2020; 21(7):2379. https://doi.org/10.3390/ijms21072379

Chicago/Turabian Style

Hymos, Anna, Ewelina Grywalska, Janusz Klatka, Maria Klatka, Izabela Korona-Głowniak, and Jacek Roliński. 2020. "ThymicPeptides Reverse Immune Exhaustion in Patients with Reactivated Human Alphaherpesvirus1 Infections" International Journal of Molecular Sciences 21, no. 7: 2379. https://doi.org/10.3390/ijms21072379

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