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T-cell subsets in the hyporesponsiveness to hepatitis B surface antigen (HBsAg) and antigen-specific suppressor lymphocytes in chronic hepatitis B virus (HBV) infection
Authors:V Barnaba  M Levrero  A D Van Dyke  A Musca  C Cordova  F Balsano
Affiliation:1. Maternal Fetal Medicine Unit, Department of Obstetrics and Gynaecology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand;2. UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction, Department of Reproductive Health and Research, WHO, Geneva, Switzerland;3. Department of Obstetrics and Gynaecology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand;4. Department of Epidemiology and Biostatistics, Khon Kaen University, Khon Kaen, Thailand;5. Health Metrics Unit, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden;6. School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa;7. Department of Information, Evidence and Research, WHO, Geneva, Switzerland;8. Joondalup Health Campus, Joondalup, WA, Australia;9. Sir Charles Gairdner Hospital, Nedlands, WA, Australia;10. Ministry of Education-Shanghai Key Laboratory of Children''s Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;1. Public Administration and Policy Group, Wageningen University, Netherlands;2. Public Policy and Governance, Management Development Institute (MDI), Gurgaon, India;1. Department of Physics, Dayanand Sagar Academy of Technology and Management, Bengaluru 560082, India;2. Research and Development Center, Bharathiar University, Coimbatore 641046, India;3. Research Center, Department of Science, East West Institute of Technology, VTU, Bengaluru 560091, India;4. Prof. CNR Rao Center for Advanced Materials, Tumkur University, Tumkur 572103, India;5. Department of Physics, New Horizon College of Engineering, Bengaluru 560103, India;6. Department of Physics, Ramaiah University of Applied Sciences, Peenya Campus, Bengaluru 560058, India;7. Department of Humanities, PVP Polytechnic, Dr. AIT Campus, Bengaluru 560056, India;1. Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA;2. Special Coagulation Laboratory, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA;3. Frontier Program in Immune Dysregulation, Division of Hematology, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA;1. Università degli Studi di Napoli Federico II, Piazzale Tecchio 80, 80125 Napoli, Italy;2. Università degli Studi del Sannio, Piazza Roma 21, 82100 Benevento, Italy
Abstract:In contrast to convalescent hepatitis B patients, who exhibit the ability to elicit a specific immune response to HBsAg, patients with chronic hepatitis B virus (HBV) infection are markedly hyporesponsive to HBsAg and show a decrease in the normal ratio of OKT4-positive (helper/inducer) to OKT8-positive (suppressor/cytotoxic) lymphocytes. In this study the role of OKT4-positive and OKT8-positive cells on cellular immune response to HBsAg was evaluated in patients with chronic HBV infection and the ability of such patients to develop antigen-specific suppressor lymphocytes after in vitro sensitization to HBsAg. Elimination of OKT8-positive cells markedly improved the in vitro lymphocyte proliferative response to HBsAg without altering the reactivity of cells from the same donor to PPD or Candida. In contrast, the degree of responsiveness to HBsAg was not affected by the depletion of OKT4-positive cells. In vitro co-culture experiments, performed in the seven chronically HBV-infected patients who showed a proliferative response when their PBM were cultured with purified HBsAg or PPD, have demonstrated that lymphocytes from chronic HBV carriers, stimulated with HBsAg, inhibit the response of autologous PBM to HBsAg but not to the unrelated antigen PPD.
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