TH1 and TH2 Responses Are Influenced by HLA Antigens in Healthy Neonates Vaccinated with Recombinant Hepatitis B Vaccine
Abstract
The immune response to hepatitis B surface antigen (HBsAg) is influenced by several factors, of which HLA antigens and balanced secretion of Th1/Th2 cytokines play important roles. The aim of this study was to evaluate the influence of HLA antigens on cytokine secretion by HBsAg-stimulated peripheral blood mononuclear cells (PBMC) from healthy neonates vaccinated with recombinant HBsAg. PBMCs were isolated from 48 Iranian neonates vaccinated with a recombinant HBV vaccine. The cells were stimulated in vitro with rHBsAg and the concentration of IL-4, IL-10, IL-12 and IFN-γ were quantitated in culture supernatant by sandwich ELISA. HLA typing was performed by microlymphocytotoxicity method. Significant diminished secretion of both Th1 (IFN-γ) and Th2 (IL-4, IL-10) cytokines was observed in HBsAg-stimulated PBMC from vaccinees expressing the HLA-DR7 compared to DR7 negative vaccinees. Similarly, lower production of these cytokines was also observed in vaccinees with DR7-DR53-DQ2, B7-DR7-DR53-DQ2 and A2-DR7-DR53-DQ2 haplotypes (p<0.05, p <0.005). While HBsAg-stimulated PBMC of DR13+ subjects produced lower levels of Th2-type cytokines (IL-4 and IL-10), those of HLA-B8+ or HLA-A9+ subjects produced higher levels of Th2-type cytokines. Cytokine secretion in response to PHA mitogen was not associated with a given HLA antigen or haplotype and was similarly represented in all groups of subjects irrespective of their HLA complex. These results indicate that HLA antigens may differentially influence cytokine secretion by HBsAg-specific T-cells of healthy neonates vaccinated with recombinant HB vaccine. This phenomenon may have an important implication for control of the immune response to HBsAg vaccine.
1. Jafarzadeh A, Zarei S, Shokri F. Low dose revaccination induces robust protective anti-HBs antibody response in the majority of healthy non-responder neonates. Vaccine 2008; 26(2):269-76.
2. Baghianimoghadam MH, Shadkam MN, Hadinedoushan H. Immunity to hepatitis B vaccine among health care workers. Vaccine 2011; 29(15):2727-9.
3. Agladioglu S, Beyazova U, Camurdan AD, Sahin F, Atak A. Immunogenicity of recombinant hepatitis B vaccine:comparison of two different vaccination schedules. Infection 2010; 38(4):269-73.
4. Desombere I, Gijbels Y, Verwulgen A, Leroux-Roels G.
Characterization of the T cell recognition of hepatitis B surface antigen (HBsAg) by good and poor responders to hepatitis B vaccines. Clin Exp Immunol 2000;122(3):390-9.
5. Jafarzadeh A, Shokrgozar MA, Khoshnoodi J, Shokri F.Unresponsiveness to recombinant hepatitis B vaccine in healthy Iranian neonates: association with HLA antigens. Irn J Med Sci 2002; 27(2):51-5.
6. Amirzargar AA, Mohseni N, Shokrgozar MA, Arjang Z, Ahmadi N, Yousefi Behzadi M, et al. HLA-DRB1, DQA1 and DQB1 alleles and haplotypes frequencies in Iranian healthy adult responders and non-responders to recombinant hepatitis B vaccine. Iran J Immunol 2008;5(2):92-9.
7. Godkin A, Davenport M, Hill AV. Molecular analysis of HLA class II associations with hepatitis B virus clearance and vaccine nonresponsiveness. Hepatology 2005;41(6):1383-90.
8. Vingerhoets J, Vanham G, Kestens L, Penne G, Leroux- Roels G, Gigase P. Deficient T-cell response in non- responders to hepatitis B vaccination: absence of TH1 cytokine production. Immunol lett 1994; 39(2):163-8.
9. Chedid MG, Deulofeut H, Yunis DE, Lara-Marquez ML, Salazar M, Deulofeut R, et al. Defect in Th1-like cells of non-responders to hepatitis B vaccine. Hum Immunol 1997; 58(1):42-51.
10. Livingston BD, Alexander J, Crimi C, Oseroff C, Celis E, Daly K, et al. Altered helper T-lymphocyte function associated with chronic hepatitis B virus infection and its role in response to therapeutic vaccination in human. J Immunol 1999; 162(5):3088-95.
11. Velu V, Saravanan S, Nandakumar S, Shankar EM,Vengatesan A, Jadhav SS, et al. Relationship between T- lymphocyte cytokine levels and sero-response to hepatitis B vaccines. World J Gastroenterol 2008; 14(22):3534-40.
12. Kardar GA, Jeddi-Tehrani M, Shokri F. Diminished Th1 and Th2 cytokine production in healthy adult non- responders to recombinant hepatitis B vaccine. Scand J Immunol 2002; 55(3):311-4.
13. Honorati MC, Dolzani P, Mariani E, Piacentini A, Lisignoli G, Ferrari C, et al. Epitope specificity of Th0/Th2 CD4+ T-lymphocyte clones induced by vaccination with rHBsAg vaccine. Gastroenterology 1997; 112(6):2017-27.
14. Ota MO, Vekemans J, Schlegel-Haueter SE, Fielding K, Whittle H, Lambert PH, et al. Hepatitis B immunization induces higher antibody and memory Th2 responses in new-borns than in adults. Vaccine 2004; 22(3-4):511-9.
15. Wataya M, Sano T, Kamikawaji N, Tana T, Yamamoto K, Sasazuki T, et al. Comparative analysis of HLA restriction and cytokine production in hepatitis B surface antigen-specific T-cells from low-and high- antibody responders in vaccinated humans. J Hum Genet 2001;46(4):197-206.
16. Jafarzadeh A, Shokri F. The antibody response to HBs antigen is regulated by coordinated Th1 and Th2 cytokine production in healthy neonates. Clin Exp Immunol 2003,131(3):451-6.
17. Shokrgozar MA, Shokri F. HLA-associated antibody response to recombinant hepatitis B vaccine in healthy Iranian adults. Irn J Med Sci 1999; 24:98-103.
18. Jafarzadeh A, Kardar GA, Khoshnoodi J, Shokri F.Downregulation of IL-12 production in healthy non- responder neonates to recombinant hepatitis B vaccine. Irn Biomed J 2004; 8(1):41-5.
19. Li Y, Ni R, Song W, Shao W, Shrestha S, Ahmad S, et al.Clear and independent associations of several HLA- DRB1 alleles with differential antibody responses to hepatitis B vaccination in youth. Hum Genet 2009;126(5):685-96.
20. Das K, Gupta RK, Kumar V, Singh S, Kar P. Association of HLA phenotype with primary non-response to recombinant hepatitis B vaccine: a study from north India. Trop Gastroenterol 2004; 25(3):113-5.
21. Fletcher GJ, Samuel P, Christdas J, Gnanamony M,Ismail AM, Anantharam R, et al. Association of HLA and TNF polymorphisms with the outcome of HBV infection in the South Indian population. Genes Immun 2011;12(7):552-8.
22. Kruger A, Adams P, Hammer J, Böcher WO, Schneider PM, Rittner C, et al. Hepatitis B surface antigen presentation and HLA-DRB1*- lessons from twins and peptide binding studies. Clin Exp Immunol 2005;140(2):325-32.
23. Desombere I, Gijbels Y, Verwulgen A. Characterization of the T cell recognition of hepatitis B surface antigen (HBsAg) by good and poor responders to hepatitis B vaccine. Clin Exp Immunol 2000; 122(3):390-9.
24. Desombere I, Cao T, Gijbels Y, Leroux-Roels G. Non- responsiveness to hepatitis B surface antigen vaccines is not caused by defective antigen presentation or a lack of B7 co-stimulation. Clin Exp Immunol 2005; 140(1):126-37.
25. Avanzini MA, Belloni C, De Silvestri A, Castellazzi AM, Marconi M, Moretta A, et al. Antigen-specific T cell response in infants after recombinant hepatitis B virus vaccination at birth: evaluation of T helper lymphocyte diversity. Clin Immunol 2003; 107(2):122-8.
26. Wataya M, Sano T, Kamikawaji N, Tana T, Yamamoto K, Sasazuki T. Comparative analysis of HLA restriction and cytokine production in hepatitis B surface antigen- specific T-cells from low-and high- antibody responders in vaccinated humans. J Hum Genet 2001; 46(4):197-206.
27. Desombere I, Cao T, Gijbels Y, Leroux-Roels G. Non- responsiveness to hepatitis B surface antigen vaccines is not caused by defective antigen presentation or a lack of B7 co-stimulation. Clin Exp Immunol 2005; 140(1):126-37.
28. Lango-Warensjo A, Cardell K, Lindblom B. Haplotypes comprising subtypes of the DQB1*06 allele directed the antibody response after immunization with hepatitis B surface antigen. Tissue antigen 1998; 52(4):374-80.
29. Liang HX, Yu ZJ, Jiang HQ. Study on the association between chronic hepatitis B cirrhosis and HLA-DRB1 *1301, 1302 allele. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi 2009; 23(4):302-3.
30. Hohler T, Gerken G, Notghi A, Lubjuhn R, Taheri H, Protzer U, et al. HLA DRB1*1301 and 1302 protect against chronic hepatitis B. J Hepatol 1997; 26(30):503-7.
31. Kummee P, Tangkijvanich P, Poovorawan Y, Hirankarn N. Association of HLA-DRB1*13 and TNF-alpha gene polymorphisms with clearance of chronic hepatitis B infection and risk of hepatocellular carcinoma in Thai population. J Viral Hepat 2007; 14(2):841-8.
32. Diepolder HW, Jung MC, Keller E, Schraut W, Gerlanch JT, Grüner N, et al. A vigorous virus-specific CD4+ T cell response may contribute to the association of HLA-DR13 with viral clearance in hepatitis. Clin Exp Immunol 1998;113(2):244-51.
33. Kacprzak-Bergman I, Nowakowska B. Influence of genetic factors on the susceptibility to HBV nfection, its clinical pictures, and responsiveness to HBV vaccination. Arch Immunol Ther Exp 2005; 53(2):139-42.
34. Candore G, Romano GC, Anna CD, Lorenzo GD,Gervasi F, Lio D, et al. Biological basis of HLA-B8, DR3-associated progression of acquired immune deficiency syndrome. Pathol 1998; 66(1):33-7.
35. Thio CL, Thomas DL, Karacki P, Gao X, Kaslow RA, Goedert JJ, et al. Comprehensive analysis of class I and classII HLA antigens and chronic hepatitis B virus infection. J Virol 2003; 77(22):12083-7.
36. Mignini F, Streccioni V, Baldo M, Vitali M, Indraccolo U, Bernacchia G. Individual susceptibility to hexavalent chromium of workers of shoe, hide, and leather industries. Immunological pattern of HLA-B8, DR3- positive subjects. Prev Med 2004; 39(4):767-75.
37. Holzer U, Kwok WW, Nepom GT, Buckner JH.Differential antigen sensitivity and costimulatory requirements in human Th1 and Th2 antigen-specific CD4+ cells with similar TCR avidity. J Immunol 2003;170(3):1218-23.
38. Kruger A, Adams P, Hammer J, Bocher WO, Schneider PM, Rittner C, et al. Hepatitis B surface antigen presentation and HLA-DRB1*- lessons from twins and peptide binding studies. Clin Exp Immunol 2005;140(2):325-32.
39. Murai M, Krause P, Cheroutre H, Kronenberg M.Regulatory T-cell stability and plasticity in mucosal and systemic immune systems. Mucosal Immunol 2010;3(5):443-9.
40. Yu H, Zhu QR, Gu SQ, Fei LE. Relationship between IFN-gamma gene polymorphism and susceptibility to intrauterine HBV infection. World J Gastroenterol 2006;12(18):2928-31.
41. Wang C, Tang J, Song W, Lobashevsky E, Wilson CM, Kaslow RA. HLA and cytokine gene polymorphisms are independently associated with responses to hepatitis B vaccination. Hepatology 2004; 39(4):978-88.
| Files | ||
| Issue | Vol 11, No 4 (2012) | |
| Section | Articles | |
| Keywords | ||
| Cytokine Hepatitis B vaccine HLA antigens | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
