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Nat Med. 2007 Jan;13(1):46-53

Evolution of the Functional Profile of HIV-Specific CD8+ T cells in a Cohort of Long Term Nonprogressors M López, N Rallón, A Peris, M Salgado, B Rodés, V Soriano, J González-Lahoz, and JM Benito Hospital Carlos III, Madrid, Spain.

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Nat Med. 2007 Jan;13(1):46-53

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  1. Evolution of the Functional Profile of HIV-Specific CD8+ T cells in a Cohort of Long Term Nonprogressors M López, N Rallón, A Peris, M Salgado, B Rodés, V Soriano, J González-Lahoz, and JM Benito Hospital Carlos III, Madrid, Spain

  2. A small proportion of HIV-subjects is able to control virus replication and halt disease progression • A higher and/or better HIV-specific immune response in these patients is believed to contribute to their favourable outcome • However, it is not well understood what characteristics of HIV-specific immune response better correlate with protection

  3. Transversal studies have suggested that a polyfunctional HIV-specific immune response and directed against Gag may be involved in the control of HIV viral replication

  4. Blood. 2006 Jun 15;107(12):4781-9 Nat Med. 2007 Jan;13(1):46-53

  5. The stability or the potential evolution over time of cellular immune response in the absence of antiretroviral therapy, especially in long term non-progressors (LTNP) has been scarcely analysed

  6. Herein, we have studied the evolution of HIV specific CD8+ T cell response in LTNP followed for four years OBJECTIVE

  7. METHODOLOGY • 10 HIV+ patients belonging to a cohort of well-characterized LTNP followed for four years were included in this study • LTNP : • Serologically proven HIV-1 infection lasting for over 10 years, • CD4 counts always above 500 cells/l and • lack of HIV-related symptoms in the absence of any antiretroviral therapy

  8. Three functions of CD8+ T-cells (production of MIP1, IL2 and TNF) were simultaneously examined in response to HIV-Gag and Nef peptide-pools using multiparameter flow cytometry

  9. MIP1β MIP1β Gag-specific CD8+ T cell responses A Lymphocytes CD8+ cells CD8+ cells TNFα- PECY7 CD8- ECD IL2-PE LTNP FS P SS

  10. All variables were expressed as median [interquartile range] • Differences between values at baseline and after four years were evaluated using non-parametric tests

  11. RESULTS

  12. CD4 count (cell/l) n Viral Load (Log ARN copies / ml) 10 2.6 [0.8] At baseline 754 [400] After 4 years of follow up 10 619 [300] 3.2 [1.6] n.s p n.s n.s: no significant difference, p>0,05 Characteristics of Patients

  13. HIV- GAG SPECIFIC CD8+ T CELL RESPONSE

  14. 4 4 At baseline At baseline After 4 years of follow up After 4 years of follow up 3 3 * p<0.05 * p<0.05 % CD8+ T cells % CD8+ T cells 2 2 1 1 0 0 Global HIV-GAG specific CD8+ T cell response in LTNPs at baseline and after 4 years of follow up

  15. 100 At baseline After 4 years of follow up Percentage of patients 50 0 MIPβ TNFα IL2 • • • • • • • • • • • • Prevalence of HIV-Gag CD8+ T cell response in LTNPs at baseline and after 4 years of follow up

  16. 3 At baseline After 4 years of follow up 2 % CD8+ T cells * p<0.05 * 1 * 0 MIPβ TNFα IL2 • • • • • • • • • • • • Levels of seven different functional subsets of CD8+ T cells in response to HIV-GAG in LTNPs at baseline and after 4 years of follow up

  17. Contribution of seven different functional subsets of CD8+ T cells to the global HIV-GAG response in LTNPs at baseline and after 4 years of follow up

  18. Contribution of seven different functional subsets of CD8+ T cells to the global HIV-GAG response in each LTNP at baseline and after 4 years of follow up

  19. HIV- NEF SPECIFIC CD8+ T CELL RESPONSE

  20. 2 At baseline After 4 years of follow up * p<0.05 % CD8+ T cells 1 0 Global HIV-NEF specific CD8+ T cell response in LTNPs at baseline and after 4 years of follow up

  21. Prevalence of HIV-Nef CD8+ T cell response in LTNPs at baseline and after 4 years of follow up

  22. Levels of seven different functional subsets of CD8+ T cells in response to HIV-Nef in LTNPs at baseline and after 4 years of follow up

  23. Contribution of seven different functional subsets of CD8+ T cells to the global HIV-NEF response in LTNPs at baseline and after 4 years of follow up

  24. Contribution of seven different functional subsets of CD8+ T cells to the global HIV-NEF response in each LTNP at baseline and after 4 years of follow up

  25. HIV-specific CD8+ responses are maintained over time in LTNP. • The functional profile of this response may evolve in a different manner depending on the targeted HIV protein. • Functionality of Gag specific CD8+ T cells tends to increase over time, highlighting its importance in controlling HIV replication. CONCLUSIONS

  26. Funding Laboratory Immunology Group Mariola López Sara Lozano Norma Ibon Rallón Alejandra Peris Clara Restrepo Jose Miguel Benito To all staff at the Molecular Biology Lab ACKNOWLEDGMENTS Clinic Juan González-Lahoz Pablo Labarga Pablo Barreiro Francisco Blanco Luz Martín-Carbonero Pablo Rivas Eugenia Vispo Jose Medrano Vicente Soriano Patients

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