Restoration of the CD4 T cell compartment after long-term highly active antiretroviral therapy without phenotypical signs of accelerated immunological aging

Journal of Immunology

Volumn 181, Issue 2, 2008, Pages 1573-1581

  Vrisekoop, Nienke ^a,b   Van Gent, Rogier ^a,b   De Boer, Anne Bregje ^a,b   Otto, Sigrid A ^a,b   Borleffs, Jan C C ^a   Steingrover, Radjin ^b,c   Prins, Jan M ^b   Kuijpers, Taco W ^d   Wolfs, Tom F W ^a   Geelen, Sibyl P M ^a   Vulto, Irma ^e   Lansdorp, Peter ^e   Tesselaar, Kiki ^a,b   Borghans, José A M ^a,f   Miedema, Frank ^a  

^a UNIVERSITY MEDICAL CENTER UTRECHT   (Netherlands)

^b ACADEMIC MEDICAL CENTER   (Netherlands)

^c Intl Antiviral Ther Eval Center   (Netherlands)

^d UNIVERSITY OF AMSTERDAM   (Netherlands)

^e BRITISH COLUMBIA CANCER AGENCY   (Canada)

^f UTRECHT UNIVERSITY   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

ABACAVIR; ANTIRETROVIRUS AGENT; CD31 ANTIGEN; PROTEINASE INHIBITOR; RNA DIRECTED DNA POLYMERASE INHIBITOR; TENOFOVIR; KI 67 ANTIGEN;

ADOLESCENT; ADULT; AGED; ANTIGEN EXPRESSION; ARTICLE; CD4 LYMPHOCYTE COUNT; CD4+ T LYMPHOCYTE; CELL AGING; CELL COMPARTMENTALIZATION; CELL COUNT; CELL DIVISION; CELL LINE; CELL PROLIFERATION; CELL SELECTION; CHILD; DISEASE MARKER; EXCISION; FLOW CYTOMETRY; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; LYMPHOCYTE COUNT; LYMPHOCYTOPOIESIS; MAJOR CLINICAL STUDY; PHENOTYPE; PRESCHOOL CHILD; PRIORITY JOURNAL; SCHOOL CHILD; T LYMPHOCYTE ACTIVATION; T LYMPHOCYTE SUBPOPULATION; THYMUS; TREATMENT DURATION; VIRUS LOAD; DRUG EFFECT; HUMAN IMMUNODEFICIENCY VIRUS 1; IMMUNOLOGY; INFANT; LYMPHOCYTE ACTIVATION; METABOLISM; MIDDLE AGED; VIROLOGY;

ADOLESCENT; ADULT; ANTIGENS, CD31; ANTIRETROVIRAL THERAPY, HIGHLY ACTIVE; CD4 LYMPHOCYTE COUNT; CD4-POSITIVE T-LYMPHOCYTES; CHILD; CHILD, PRESCHOOL; HIV INFECTIONS; HIV-1; HUMANS; INFANT; KI-67 ANTIGEN; LYMPHOCYTE ACTIVATION; MIDDLE AGED; T-LYMPHOCYTE SUBSETS;

EID: 49049112514     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.181.2.1573     Document Type: Article

References (52)

1. Hunt, P. W., S. G. Deeks, B. Rodriguez, H. Valdez, S. B. Shade, D. I. Abrams, M. M. Kitahata, M. Krone, T. B. Neilands, R. J. Brand, et al. 2003. Continued CD4 cell count increases in HIV-infected adults experiencing 4 years of viral suppression on antiretroviral therapy. AIDS 17: 1907-1915.
2. Kaufmann, G. R., H. Furrer, B. Ledergerber, L. Perrin, M. Opravil, P. Vernazza, M. Cavassini, E. Bernasconi, M. Rickenbach, B. Hirschel, and M. Battegay. 2005. Characteristics, determinants, and clinical relevance of CD4 T cell recovery to <500 cells/μL in HIV type 1-infected individuals receiving potent antiretroviral therapy. Clin. Infect. Dis. 41: 361-372.
3. + T-cell count. J. Acquir. Immune. Defic. Syndr. 36: 702-713.
4. + T-lymphocyte regeneration after intensive chemotherapy. N. Engl. J. Med. 332: 143-149.
5. Sleasman, J. W., R. P. Nelson, M. M. Goodenow, D. Wilfret, A. Hutson, M. Baseler, J. Zuckerman, P. A. Pizzo, and B. U. Mueller. 1999. Immunoreconstitution after ritonavir therapy in children with human immunodeficiency virus infection involves multiple lymphocyte lineages. J. Pediatr. 134: 597-606.
6. Van Rossum, A. M. C., H. J. Scherpbier, E. G. Van Lochem, N. G. Pakker, W. A. T. Slieker, K. C. Wolthers, M. T. L. Roos, J. H. S. A. M. Kuijpers, H. Hooijkaas, N. G. Hartwig, et al. 2001. Therapeutic immune reconstitution in HIV-1 infected children treated with highly active antiretroviral therapy is independent of their age and pretreatment immunestatus. AIDS 15: 2267-2275.
7. + T lymphocyte regeneration after anti-retroviral therapy in HIV-1 infected children and adult patients. Clin. Exp. Immunol. 119: 493-498.
8. Resino, S., E. Seoane, A. Perez, E. Ruiz-Mateos, M. Leal, and M. A. Munoz-Fernandez. 2006. Different profiles of immune reconstitution in children and adults with HIV-infection after highly active antiretroviral therapy. BMC Infect. Dis. 6: 112. (Pubitemid 44227544)
9. Grabar, S., I. Kousignian, A. Sobel, B. P. Le, J. Gasnault, P. Enel, C. Jung, A. Mahamat, J. M. Lang, and D. Costagliola. 2004. Immunologic and clinical responses to highly active antiretroviral therapy over 50 years of age: results from the French Hospital Database on HIV. AIDS 18: 2029-2038. (Pubitemid 39463356)
10. Teixeira, L., H. Valdez, J. M. McCune, R. A. Koup, A. D. Badley, M. K. Hellerstein, L. A. Napolitano, D. C. Douek, G. Mbisa, S. Deeks, et al. 2001. Poor CD4 T cell restoration after suppression of HIV-1 replication may reflect lower thymic function. AIDS 15: 1749-1756. (Pubitemid 32939234)
11. Ruiz-Mateos, E., R. de la Rosa, N. Soriano, M. Martinez-Moya, A. Rubio, A. Sanchez-Quijano, E. Lissen, and M. Leal. 2003. Comparison of thymic function- related markers to predict early CD4 T-cell repopulation in adult HIV-infected patients on HAART. Antivir. Ther. 8: 289-294. (Pubitemid 37101631)
12. Resino, S., R. Correa, J. M. Bellon, S. Sanchez-Ramon, and M. A. Munoz-Fernandez. 2002. Characterizing immune reconstitution after longterm highly active antiretroviral therapy in pediatric AIDS. AIDS Res. Hum. Retroviruses 18: 1395-1406. (Pubitemid 36044744)
13. Vigano, A., S. Vella, M. Saresella, A. Vanzulli, D. Bricalli, S. Di Fabio, P. Ferrante, M. Andreotti, M. Pirillo, L. G. Dally, et al. 2000. Early immune reconstitution after potent antiretroviral therapy in HIV-infected children correlates with the increase in thymus volume. AIDS 14: 251-261. (Pubitemid 30132919)
14. Clerici, M., M. Saresella, D. Trabattoni, P. Ferrante, A. Vanzulli, and A. Vigano. 2002. Thymic volume predicts long-term immune reconstitution in HIV-infected children treated with highly active antiretroviral therapy. AIDS 16: 2219-2221. (Pubitemid 35387277)
15. Kolte, L., A. M. Dreves, A. K. Ersboll, C. Strandberg, D. L. Jeppesen, J. O. Nielsen, L. P. Ryder, and S. D. Nielsen. 2002. Association between larger thymic size and higher thymic output in human immunodeficiency virus-infected patients receiving highly active antiretroviral therapy. J. Infect. Dis. 185: 1578-1585. (Pubitemid 34587519)
16. + cells in HIV-1-infected patients receiving highly active antiretroviral therapy who have prolonged undetectable plasma viral loads. J. Infect. Dis. 191: 1670-1679.
17. Douek, D. C., R. D. McFarland, P. H. Keiser, E. A. Gage, J. M. Massey, B. F. Haynes, M. A. Polis, A. T. Haase, M. B. Feinberg, J. L. Sullivan, et al. 1998. Changes in thymic function with age and during the treatment of HIV infection. Nature 396: 690-695. (Pubitemid 29003949)
18. Hazenberg, M. D., S. A. Otto, J. W. T. Cohen Stuart, M. C. M. Verschuren, J. C. C. Borleffs, C. A. B. Boucher, R. A. Coutinho, J. M. A. Lange, T. F. Rinke de Wit, A. Tsegaye, et al. 2000. Increased cell division but not thymic dysfunction rapidly affects the TREC content of the naive T cell population in HIV-1 infection. Nat. Med. 6: 1036-1042.
19. Anthony, K. B., C. Yoder, J. A. Metcalf, R. DerSimonian, J. M. Orenstein, R. A. Stevens, J. Falloon, M. A. Polis, H. C. Lane, and I. Sereti. 2003. Incomplete CD4 T cell recovery in HIV-1 infection after 12 months of highly active antiretroviral therapy is associated with ongoing increased CD4 T cell activation and turnover. J. Acquir. Immune. Defic. Syndr. 33: 125-133.
20. + T cell gains in human immunodeficiency virus-infected patients with sustained viral suppression during antiretroviral therapy. J. Infect. Dis. 187: 1534-1543.
21. Smith, K., E. Aga, R. J. Bosch, H. Valdez, E. Connick, A. Landay, D. Kuritzkes, B. H. Gross, I. R. Francis, J. M. McCune, et al. 2004. Long-term changes in circulating CD4 T lymphocytes in virologically suppressed patients after 6 years of highly active antiretroviral therapy. AIDS 18: 1953-1956. (Pubitemid 39313212)
22. Valdez, H., E. Connick, K. Y. Smith, M. M. Lederman, R. J. Bosch, R. S. Kim, M. St. Clair, D. R. Kuritzkes, H. Kessler, L. Fox, et al. 2002. Limited immune restoration after 3 years' suppression of HIV-1 replication in patients with moderately advanced disease. AIDS 16: 1859-1866.
23. Hazenberg, M. D., J. W. T. Cohen Stuart, S. A. Otto, J. C. C. Borleffs, C. A. Boucher, R. J. De Boer, F. Miedema, and D. Hamann. 2000. T cell division in human immunodeficiency virus (HIV-1)-infection is mainly due to immune activation: a longitudinal analysis in patients before and during highly active anti-retroviral therapy. Blood 95: 249-255.
24. Resino, S., I. Galan, A. Perez, J. A. Leon, E. Seoane, D. Gurbindo, and M. A. Munoz-Fernandez. 2004. HIV-infected children with moderate/severe immune- suppression: changes in the immune system after highly active antiretroviral therapy. Clin. Exp. Immunol. 137: 570-577. (Pubitemid 39128085)
25. Chavan, S., B. Bennuri, M. Kharbanda, A. Chandrasekaran, S. Bakshi, and S. Pahwa. 2001. Evaluation of T cell receptor gene rearrangement excision circles after antiretroviral therapy in children infected with human immunodeficiency virus. J. Infect. Dis. 183: 1445-1454. (Pubitemid 32417696)
26. Ostrowski, S. R., T. L. Katzenstein, P. T. Thim, B. K. Pedersen, J. Gerstoft, and H. Ullum. 2005. Low-level viremia and proviral DNA impede immune reconstitution in HIV-1-infected patients receiving highly active antiretroviral therapy. J. Infect. Dis. 191: 348-357. (Pubitemid 40139759)
27. Delobel, P., M. T. Nugeyre, M. Cazabat, K. Sandres-Saune, C. Pasquier, L. Cuzin, B. Marchou, P. Massip, R. Cheynier, F. Barre-Sinoussi, et al. 2006. Naive T-cell depletion related to infection by X4 human immunodeficiency virus type 1 in poor immunological responders to highly active antiretroviral therapy. J. Virol. 80: 10229-10236. (Pubitemid 44522616)
28. Patel, D. D., M. E. Gooding, R. E. Parrott, K. M. Curtis, B. F. Haynes, and R. H. Buckley. 2000. Thymic function after hematopoietic stem-cell transplantation for the treatment of severe combined immunodeficiency. N. Engl. J. Med. 342: 1332.
29. Storek, J., A. Joseph, G. Espino, M. A. Dawson, D. C. Douek, K. M. Sullivan, M. E. D. Flowers, P. Martin, G. Mathioudakis, R. A. Nash, et al. 2001. Immunity of patients surviving 20 to 30 years after allogeneic or syngeneic bone marrow transplantation. Blood 98: 3505-3512.
30. Fujimaki, K., A. Maruta, M. Yoshida, F. Kodama, M. Matsuzaki, S. Fujisawa, H. Kanamori, and Y. Ishigatsubo. 2001. Immune reconstitution assessed during five years after allogeneic bone marrow transplantation. Bone Marrow Transplant. 27: 1275-1281. (Pubitemid 32655395)
31. Sarzotti, M., D. D. Patel, X. Li, D. A. Ozaki, S. Cao, S. Langdon, R. E. Parrott, K. Coyne, and R. H. Buckley. 2003. T cell repertoire development in humans with SCID after nonablative allogeneic marrow transplantation. J. Immunol. 170: 2711-2718. (Pubitemid 36245665)
32. Borghans, J. A., R. G. Bredius, M. D. Hazenberg, H. Roelofs, E. C. Jol-van der Zijde, J. Heidt, S. A. Otto, T. W. Kuijpers, W. E. Fibbe, J. M. Vossen, et al. 2006. Early determinants of long-term T-cell reconstitution after hematopoietic stem cell transplantation for severe combined immunodeficiency. Blood 108: 763-769. (Pubitemid 44061382)
33. Hazenberg, M. D., S. A. Otto, E. S. De Pauw, H. Roelofs, W. E. Fibbe, D. Hamann, and F. Miedema. 2002. T cell receptor excision circle (TREC) and T cell dynamics after allogeneic stem cell transplantation are related to clinical events. Blood 99: 3449-3453.
34. Weinberg, K., B. R. Blazar, J. E. Wagner, E. Agura, B. J. Hill, M. Smogorzewska, R. A. Koup, M. R. Betts, R. H. Collins, and D. C. Douek. 2001. Factors affecting thymic function after allogeneic hematopoietic stem cell transplantation. Blood 97: 1458-1466. (Pubitemid 32183773)
35. Shand, J. C., P. J. Mansky, M. V. Brown, T. A. Fleisher, and C. L. Mackall. 2006. Adolescents and young adults successfully restore lymphocyte homeostasis after intensive T-cell depleting therapy for cancer. Br. J. Haematol. 135: 270-271.
36. + T-cell recovery are associated with efficient thymopoiesis during HIV-1 infection. Blood 109: 2912-2920.
37. Pongers-Willemse, M. J., O. J. H. M. Verhagen, G. J. M. Tibbe, A. J. M. Wijkhuijs, V. De Haas, E. Roovers, C. E. Van der Schoot, and J. J. M. Van Dongen. 1998. Real-time quantitative PCR for the detection of minimal residual disease in acute lymphoblastic leukemia using junctional region specific TaqMan probes. Leukemia 12: 2006-2014.
38. Dutilh, B. E., and R. J. De Boer. 2003. Decline in excision circles requires homeostatic renewal or homeostatic death of naive T cells. J. Theor. Biol. 224: 351-358.
39. Shearer, W. T., H. M. Rosenblatt, R. S. Gelman, R. Oyomopito, S. Plaeger, E. R. Stiehm, D. W. Wara, S. D. Douglas, K. Luzuriaga, E. J. McFarland, et al. 2003. Lymphocyte subsets in healthy children from birth through 18 years of age: the Pediatric AIDS Clinical Trials Group P1009 study. J. Allergy Clin. Immunol. 112: 973-980.
40. Bofill, M., G. Janossy, C. A. Lee, D. Donald-Burns, A. N. Phillips, C. Sabin, A. Timms, M. A. Johnson, and P. B. Kernoff. 1992. Laboratory control values for CD4 and CD8 T lymphocytes: implications for HIV-1 diagnosis. Clin. Exp. Immunol. 88: 243-252.
41. + T cells constrains the TCR repertoire in healthy human adults. Eur. J. Immunol. 35: 1987-1994.
42. Kimmig, S., G. K. Przybylski, C. A. Schmidt, K. Laurisch, B. Mowes, A. Radbruch, and A. Thiel. 2002. Two subsets of naive T helper cells with distinct T cell receptor excision circle content in human adult peripheral blood. J. Exp. Med. 195: 789-794. (Pubitemid 34259723)
43. 3 or greater. J. Acquir. Immune. Defic. Syndr. 45: 183-192.
44. + T cell after highly active antiretroviral therapy. J. Clin. Immunol. 24: 379-388.
45. Ometto, L., D. De Forni, F. Patiri, V. Trouplin, F. Mammano, V. Giacomet, C. Giaquinto, D. Douek, R. Koup, and A. De Rossi. 2002. Immune reconstitution in HIV-1-infected children on antiretroviral therapy: role of thymic output and viral fitness. AIDS 16: 839-849. (Pubitemid 34409007)
46. De Rossi, A., A. S. Walker, N. Klein, D. De Forni, D. King, and D. M. Gibb. 2002. Increased thymic output after initiation of antiretroviral therapy in human immunodeficiency virus type 1-infected children in the Paediatric European Network for Treatment of AIDS (PENTA) 5 Trial. J. Infect. Dis. 186: 312-320. (Pubitemid 34816314)
47. Al-Harthi, L., J. Voris, B. K. Patterson, S. Becker, J. Eron, K. Y. Smith, R. D'Amico, D. Mildvan, J. Snidow, B. Pobiner, et al. 2004. Evaluation of the impact of highly active antiretroviral therapy on immune recovery in antiretroviral naive patients. HIV Med. 5: 55-65. (Pubitemid 38219983)
48. Vigano, A., L. Dally, D. Bricalli, N. Sala, M. Pirillo, M. Saresella, D. Trabattoni, S. Vella, M. Clerici, and N. Principi. 1999. Clinical and immuno-virologic characterization of the efficacy of stavudine, lamivudine, and indinavir in human immunodeficiency virus infection. J. Pediatr. 135: 675-682. (Pubitemid 30180414)
49. Resino, S., I. Galan, J. M. Bellon, M. L. Navarro, J. A. Leon, and M. A. Munoz-Fernandez. 2003. Characterizing the immune system after longterm undetectable viral load in HIV-1-infected children. J. Clin. Immunol. 23: 279-289. (Pubitemid 36880746)
50. Douek, D. C., R. A. Koup, R. D. McFarland, J. L. Sullivan, and K. Luzuriaga. 2000. Effect of HIV on thymic function before and after antiretroviral therapy in children. J. Infect. Dis. 181: 1479-1482. (Pubitemid 30252560)
51. Hazenberg, M. D., J. A. Borghans, R. J. De Boer, and F. Miedema. 2003. Thymic output: a bad TREC record. Nat. Immunol. 4: 97-99.
52. De Boer, R. J., and A. J. Noest. 1998. T cell renewal rates, telomerase, and telomere length shortening. J. Immunol. 160: 5832-5837.