Detection of specific memory lymphocytes against HPV-16 in men and women with active sexual life
Detección de linfocitos de memoria específicos contra el VPH-16 en hombres y mujeres con vida sexual activa
Show authors biography
In this work we investigated the response of memory lymphocytes and the identification of peptides in the human papillomavirus (HPV) Ll protein responsible for the stimulation of these lymphocytes, in blood samples from 44 individuals exposed to the infection, distributed in four groups: healthy women, sex workers, patients with intracervical necrosis NIC and men. The in vitro expansion with interleukin-2 (IL-2) represented an important advantage to demonstrate the response of memory lymphocytes, specific against the virus in the majority of individuals studied. To investigate the status of the response of these lymphocytes, autologous dendritic cells (CDs) pulsed with pseudo viral particles (VLPs) constructed from the Ll protein of HPV-16 [VPL-16 / L1 VLPs] as host-presenting cells were used. antigen (APCs). The use of CDs as APCs in this study allowed us to demonstrate on the one hand a vigorous production of IFN-y by memory lymphocytes in the majority of individuals studied and on the other hand to discover a suppressor phenotype induced by CDs in the response of memory lymphocytes , specific against the detectable virus, especially in patients with CIN. The universality of the cellular immune response to Ll protein, evidenced in our results, perhaps explains the high protective efficacy shown by vaccines based on VPL-161L1 VLPs, in experimentation by other researchers.
Abreviations used in the text: human papillomavirus (HPV); pseudo viral particles (VLPs); VLPs constructed from the HPV serotype 16 protein Ll (VPL-161L1 VLPs); peripheral blood lymphocytes (PBLs); stimulation index (IE); intra cervical neoplasia (CIN); antigen presenting cells (APCs); interleukin-2 (IL-2), human dendritic cells derived from peripheral blood monocytes (CDs). T lymphocyte cell line specific against IL-2 dependent VLPs (TCLs).
Article visits 523 | PDF visits 2650
Downloads
1. Zur Hausen H. Papillomaviruses and cancer: from basic studies to clinical application. Nat Rev. Cancer 2002; 2 (5):342-50.
2. Galloway DA. Papillomavirus vaccines in clinical trials. Lancet Infect Dis 2003; 3(8):469-75.
3. Koutsky LA, Ault KA, Wheeler CM, et al. Proof of Principle Study Investigators. A controlled trial of a humanpapillomavirus type 16 vaccine. N Engl J Med 2002; 347(21):1645-51.
4. Jansen KU, Shaw AR. Human papillomavirus vaccines and prevention of cervical cancer. Annu Rev Med 2004; 55:319- 31. Review.
5. Pinto LA, Edwards J, Castle PE, et al. Cellular immune responses to human papillomavirus (VPH)-16 Ll in healthy volunteers immunized with recombinant VPH-16 L1 viruslike particles. J Infect Dis 2003; 188(2):327-38.
6. Finnen RL, Erickson KD, Chen XS, Garcea RL. Interactions between papillomavirus Ll and L2 capsid proteins. J Virol 2003, 77 (8):4818-26.
7. Chen XS, Garcea RL, Goldberg I, Casini G, Harrison SC. Structure of small virus-like particles assembled from the Ll protein ofhuman papillomavirus 16. Mol Cell 2000; 5 (3):557-67.
8. Carter JJ, Wipf GC, Benki SF, Christensen ND, Galloway DA. Identification of a human papillomavirus type 16-specific epitope on the C-terminal arm of the major capsid protein Ll. J Virol 2003;77 (21):11625-32.
9. Viscidi RP, Ahdieh-Grant L, Schneider MF, et al. Serum immunoglobulin A response to human papillomavirus type 16 virus-like particles in human immunodeficiency virus (HIV)-positive and high-risk HIV-negative women. J. Infect. Dis 2003;188 (12):1834-44.
10. Vera-Bravo R, Ocampo M, Urquiza M, Garcia JE, et al. Human papillomavirus type 16 and 18 Ll protein peptide binding to VERO and HeLa cells inhibits their VLPs binding. Int J Cancer 2003; 107 (3):416-24.
11. Christensen ND, Reed CA, Cladel NM, Hall K, Leiserowitz GS. Monoclonal antibodies to VPH-6 L1 virus-like particles identify conformational and linear neutralizing epitops on VPH-11 in addition to type-specific epitopes on VPH-6. Virology 1996; 224 (2):477-86.
12. Molano M, Posso H, Weiderpass E. et al. VPH Study Group VPH Study. Prevalence and determinants of VPH infection among Colombian women with normal cytology. Br J Cancer 2002; 87 (3):324-33.
13. Combita AL, Bravo MM, Touze A, Orozco O, Coursaget P. Serologic response to human oncogenic papillomavirus types 16, 18, 31, 33, 39, 58 and 59 virus-like particles in colombian women with invasive cervical cancer. Int J Cancer 2002; 97 (6):796-803.
14. Delgado Parra-Lopez CA, Vargas LE, et al. Characterizing cellular immune response to kinetoplastid membrane protein-11 (KMP-11) during Leishmania (Viannia) panamensis infection using dendritic cells (DCs) as antigen presenting cells (APCs). Parasite. Immunol 2003; 25 (4):199-20.
15. Calvo-Calle JM, Hammer J, Sinigaglia F, Clavijo P, Moya-Castro ZR, Nardin EH. Binding of malaria T cell epitops to DR and DQ molecules in vitro correlates with immunogenicity in vivo: identification of a universal T cell epitopes in the Plasmodium falcipamm circumsporozoite protein. J Immunol 1997; 159 (3):1362-73.
16. Sprent J, Surh CD. T cell memory. Annu. Rev Immunol 2002; 20:551-79.
17. Reece WH, Pinder M, Gothard PK, et al. ACD4 (+) T-cell immune response to a conserved epitope in the circumsporozoite protein correlates with protection from natural Plasmodium falciparum infection and disease. Nat. Med 2004;10 (4):406-10.
18. Stone KM, Karem KL, Stemberg MR, McQuillan GM, Poon AD, Unger ER, Reeves WC. Seroprevalence of human papillomavirus type 16 infection in the United States. J Infect Dis 2002; 186 (10):1396-402.
19. Lenz P, Day PM, Pang YY, Frye SA, Jensen PN, Lowy DR, Schiller JT. Papillomavirus-like particles induce acute activation ofdendritic cells. J Immunol 2001; 166 (9):5346-55.
20. Vargas LE, Parra CA, Salazar LM, Guzman F, Pinto M, Patarroyo ME. MHC allele-specific binding of a malaria peptide makes it become promiscuous on fitting a glycine residue into pocket 6. Biochem Biophys Res Commun 2003; 307 (1):148-56.
Information
Keywords
