ROLE OF HEPATITIS C VIRUS COINFECTION IN VIOLATION OF PRODUCTIVE THYMIC FUNCTION IN HIV-INFECTED PATIENTS UNDER IMMUNOLOGICALLY INEFFICIENT ANTIRETROVIRAL THERAPY
https://doi.org/10.15789/1563-0625-2013-6-543-552
Abstract
Abstract. The role of hepatitis C virus (HCV) co-infection in violation of restoring CD4+T cells in HIVinfected patients receiving antiretroviral therapy (ART) was investigated. Seventy eight patients with effective virological response to ART (viral load < 50 copies/ml) who either had or had no good immunological CD4+Tcell response after two years of treatment were recruited. Twenty one relatively healthy volunteers served as controls. The numbers of main T-lymphocyte populations and their apoptosis rates were determined. Thymus productive function was assessed by the number of αTREC-positive CD4+ and CD8+T cells. It is shown that HIV/HCV co-infection is characterized by lower numbers of CD4+T-lymphocytes in patients’ blood compared with HIV-monoinfection. This is not associated with the cells’ increased death rates. We also demonstrate that HCV coinfection reduces the production of CD4+, but not CD8+T-lymphocytes, by the thymus.
About the Authors
E. V. Saidakova
Institute of Ecology and Genetics of Microorganisms, Russian Academy of Sciences, Ural branch, Perm
Russian Federation
Russian Federation
PhD candidate, Laboratory of Ecological Immunology
614081, Goleva str., 13. Phone: 7 (342) 280-83-34. Fax: 7 (342) 280-92-11
L. B. Korolevskaya
Institute of Ecology and Genetics of Microorganisms, Russian Academy of Sciences, Ural branch, Perm
Russian Federation
Russian Federation
PhD (Medicine), Research Associate, Laboratory of Ecological Immunology
N. G. Shmagel
Perm Regional Center for Protection against AIDS and Infectious Diseases, Perm
Russian Federation
PhD (Medicine), Clinical immunologist
Russian Federation
PhD (Medicine), Clinical immunologist
K. V. Shmagel
Institute of Ecology and Genetics of Microorganisms, Russian Academy of Sciences, Ural branch, Perm
Russian Federation
Russian Federation
PhD, MD (Medicine), Deputy Director for Research
V. A. Chereshnev
Institute of Immunology and Physiology, Russian Academy of Sciences, Ural branch, Ekaterinburg
Russian Federation
Russian Federation
PhD, MD (Medicine), Professor, Full Member of Russian Academy of Sciences and Russian Academy of Medical Science, Director
References
1. ВИЧ-инфекция. Информационный бюллетень № 36. – М., Федеральный научно-методический центр по профилактике и борьбе со СПИДом, 2012. VICH-infektsiya. Informatsionnyy byulleten` № 36 [HIV-infection. Newsletter number 36]. Moscow Federal Research and Methodological Center for the Prevention and Control of AIDS, 2012. 53 p.
2. Шмагель Н.Г., Шмагель К.В., Черешнев В.А. Клинические аспекты неэффективности высокоактивной антиретровирусной терапии // Инфекционные болезни. – 2011. – Т. 9, № 1. – С. 5-10. Shmagel N.G., Shmagel K.V., Chereshnev V.A. Klinicheskie aspekty neeffektivnosti vysokoaktivnoy antiretrovirusnoy terapii [Clinical aspects of inefficiency of highly active antiretroviral therapy]. Infektsionnye bolezni – Infectious Diseases, 2011, vol. 9, no. 1, pp. 5-10.
3. Flynn J.K., Dore G.J., Matthews G., Hellard M., Yeung B., Rawlinson W.D., White P.A., Kaldor J.M., Lloyd A.R., Ffrench R.A., ATAHC Study Group. Impaired hepatitis C virus (HCV)-specific interferon-γ responses in individuals with HIV who acquire HCV infection: correlation with CD4(+) T-cell counts. J. Infect. Dis., 2012, vol. 206, pp. 1568-1576.
4. Gazzola L., Tincati C., Bellistrì G.M., Monforte Ad., Marchetti G. The absence of CD4+ T cell count recovery despite receipt of virologically suppressive highly active antiretroviral therapy: clinical risk, immunological gaps, and therapeutic options. AIDS, 2009, vol. 48, pp. 328-337.
5. Autran B. Effects of antiretroviral therapy on immune reconstitution. Antivir. Ther., 1999, vol. 4, pp. 3-6.
6. Finkel T.H., Tudor-Williams G., Banda N.K., Cotton M.F., Curiel T., Monks C., Baba T.W., Ruprecht R.M., Kupfer A. Apoptosis occurs predominantly in bystander cells and not in productively infected cells of HIV- and SIV-infected lymph nodes. Nat. Med., 1995, vol. 1, pp. 129-134.
7. Pakker N.G., Notermans D.W., de Boer R.J., Roos M.T., de Wolf F., Hill A., Leonard J.M., Danner S.A., Miedema F., Schellekens P.T. Biphasic kinetics of peripheral blood T cells after triple combination therapy in HIV-1 infection: a composite of redistribution and proliferation. Nat. Med., 1998, vol. 4, pp. 208-214.
8. Haynes B.F., Markert M.L., Sempowski G.D., Patel D.D., Hale L.P. The role of the thymus in immune reconstitution in aging, bone marrow transplantation, and HIV-1 infection. Annu Rev. Immunol., 2000, vol. 18, pp. 529-560.
9. McCune J.M. Thymic function in HIV-1 disease. Semin. Immunol., 1997, vol. 9, pp. 397-404.
10. Robbins G.K., Spritzler J.G., Chan E.S., Asmuth D.M., Gandhi R.T., Rodriguez B.A., Skowron G., Skolnik P.R., Shafer R.W., Pollard R.B., AIDS Clinical Trials Group 384 Team. Incomplete reconstitution of T cell subsets on combination antiretroviral therapy in the AIDS Clinical Trials Group protocol 384. Clin. Infect. Dis., 2009, vol. 48, pp. 350-361.
11. Gonzalez V.D., Falconer K., Blom K.G., Reichard O., M rn B., Laursen A.L., Weis N., Alaeus A., Sandberg J.K. High levels of chronic immune activation in the T-cell compartments of patients coinfected with hepatitis C virus and human immunodeficiency virus type 1 and on highly active antiretroviral therapy are reverted by alpha interferon and ribavirin treatment. J. Virol., 2009, vol. 21, pp. 11407-11141.
12. Gougeon M.L., Montagnier L. Apoptosis in AIDS. Science., 1993, vol. 260, pp. 1269-1270.
13. Jiao Y., Fu J., Xing S., Fu B., Zhang Z., Shi M., Wang X., Zhang J., Jin L., Kang F., Wu H., Wang F.S. The decrease of regulatory T cells correlates with excessive activation and apoptosis of CD8+ T cells in HIV-1-infected typical progressors, but not in long-term non-progressors. Immunology, 2009, vol. 128, pp. e366-375.
14. Lewis D.E., Gross K.L., Diez M.M., Martinez M.L., Lukefahr H.N., Kozinetz C.A., Arduino R.C. CD8 apoptosis may be a predictor of T cell number normalization after immune reconstitution in HIV. Journal of Translational Medicine, 2007, vol. 5, pp. 9-21.
15. Douek D.C., McFarland R.D., Keiser P.H., Gage E.A., Massey J.M., Haynes B.F., Polis M.A., Haase A.T., Feinberg M.B., Sullivan J.L., Jamieson B.D., Zack J.A., Picker L.J., Koup R.A. Changes in thymic function with age and during the treatment of HIV infection. Nature, 1998, vol. 396, pp. 690-695.
16. Teixeira L., Valdez H., McCune J.M., Koup R.A., Badley A.D., Hellerstein M.K., Napolitano L.A., Douek D.C., Mbisa G., Deeks S., Harris J.M., Barbour J.D., Gross B.H., Francis I.R., Halvorsen R., Asaad R., Lederman M.M. Poor CD4 T cell restoration after suppression of HIV-1 replication may reflect lower thymic function. AIDS, 2001, vol. 15, pp. 1749-1756.
17. Douek D.C., Betts M.R., Hill B.J., Little S.J., Lempicki R., Metcalf J.A., Casazza J., Yoder C., Adelsberger J.W., Stevens R.A., Baseler M.W., Keiser P., Richman D.D., Davey R.T., Koup R.A. Evidence for increased T cell turnover and decreased thymic output in HIV infection. J. Immunol., 2001, vol. 167, pp. 6663-6668.
18. Zhang J., Randall G., Higginbottom A., Monk P., Rice C.M., McKeating J.A. CD81 is required for hepatitis C virus glycoprotein-mediated viral infection. J. Virol., 2004, vol. 78, pp. 1448-1455.
19. Todd S.C., Lipps S.G., Crisa L., Salomon D.R., Tsoukas C.D. CD81 expressed on human thymocytes mediates integrin activation and interleukin 2-dependent proliferation. J. Exp. Med., 1996, vol. 184, pp. 2055-2060.
20. Kondo Y., Machida K., Liu H.M., Ueno Y., Kobayashi K., Wakita T., Shimosegawa T., Lai M.M. Hepatitis C virus infection of T cells inhibits proliferation and enhances fas-mediated apoptosis by downregulating the expression of CD44 splicing variant 6. J. Infect. Dis., 2009, vol. 199, pp. 726-736.
Review
For citations:
Saidakova E.V., Korolevskaya L.B., Shmagel N.G., Shmagel K.V., Chereshnev V.A. ROLE OF HEPATITIS C VIRUS COINFECTION IN VIOLATION OF PRODUCTIVE THYMIC FUNCTION IN HIV-INFECTED PATIENTS UNDER IMMUNOLOGICALLY INEFFICIENT ANTIRETROVIRAL THERAPY. Medical Immunology (Russia). 2013;15(6):543-552. (In Russ.) https://doi.org/10.15789/1563-0625-2013-6-543-552
Views:
978
Email this article 