1887

Abstract

depletion of CD8 T cells results in an increase in viral load in macaques chronically infected with simian immunodeficiency virus (SIVmac239Δnef). Here, the cellular and humoral immune responses associated with this transient period of enhanced viraemia in macaques infected with SIVmac239Δnef were characterized. Fourteen days after CD8 T-cell depletion, two of six macaques experienced a 1–2 log increase in anti-gp130 and p27 antibody titres and a three- to fivefold increase in gamma interferon-secreting SIV-specific CD8 T cells. Three other macaques had modest or no increase in anti-gp130 antibodies and significantly lower titres of anti-p27 antibodies, with minimal induction of functional CD8 T cells. Four of the five CD8-depleted macaques experienced an increase in neutralizing antibody titres to SIVmac239. Induction of SIV-specific immune responses was associated with increases in CD8 T-cell proliferation and fluctuations in the levels of signal-joint T-cell receptor excision circles in peripheral blood cells. Five months after CD8 T-cell depletion, only the two high-responding macaques were protected from intravenous challenge with pathogenic SIV, whilst the remaining animals were unable to control replication of the challenge virus. Together, these findings suggest that a transient period of enhanced antigenaemia during chronic SIV infection may serve to augment virus-specific immunity in some, but not all, macaques. These findings have relevance for induction of human immunodeficiency virus (HIV)-specific immune responses during prophylactic and therapeutic vaccination and for immunological evaluation of structured treatment interruptions in patients chronically infected with HIV-1.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.81206-0
2005-12-01
2019-11-12
Loading full text...

Full text loading...

/deliver/fulltext/jgv/86/12/3375.html?itemId=/content/journal/jgv/10.1099/vir.0.81206-0&mimeType=html&fmt=ahah

References

  1. Almond, N., Rose, J., Sangster, R., Silvera, P., Stebbings, R., Walker, B. & Stott, E. J. ( 1997; ). Mechanisms of protection induced by attenuated simian immunodeficiency virus. I. Protection cannot be transferred with immune serum. J Gen Virol 78, 1919–1922.
    [Google Scholar]
  2. Baba, T. W., Jeong, Y. S., Pennick, D., Bronson, R., Greene, M. F. & Ruprecht, R. M. ( 1995; ). Pathogenicity of live, attenuated SIV after mucosal infection of neonatal macaques. Science 267, 1820–1825.[CrossRef]
    [Google Scholar]
  3. Baba, T. W., Liska, V., Khimani, A. H. & 8 other authors ( 1999; ). Live attenuated, multiply deleted simian immunodeficiency virus causes AIDS in infant and adult macaques. Nat Med 5, 194–203.[CrossRef]
    [Google Scholar]
  4. Barouch, D. H., Santra, S., Schmitz, J. E. & 26 other authors ( 2000; ). Control of viremia and prevention of clinical AIDS in rhesus monkeys by cytokine-augmented DNA vaccination. Science 290, 486–492.[CrossRef]
    [Google Scholar]
  5. Chakrabarti, L. A., Lewin, S. R., Zhang, L. & 7 other authors ( 2000; ). Normal T-cell turnover in sooty mangabeys harboring active simian immunodeficiency virus infection. J Virol 74, 1209–1223.[CrossRef]
    [Google Scholar]
  6. Connor, R. I., Montefiori, D. C., Binley, J. M. & 8 other authors ( 1998; ). Temporal analyses of virus replication, immune responses, and efficacy in rhesus macaques immunized with a live, attenuated simian immunodeficiency virus vaccine. J Virol 72, 7501–7509.
    [Google Scholar]
  7. Douek, D. C., McFarland, R. D., Keiser, P. H. & 11 other authors ( 1998; ). Changes in thymic function with age and during the treatment of HIV infection. Nature 396, 690–695.[CrossRef]
    [Google Scholar]
  8. Egan, M. A., Charini, W. A., Kuroda, M. J. & 10 other authors ( 2000; ). Simian immunodeficiency virus (SIV) gag DNA-vaccinated rhesus monkeys develop secondary cytotoxic T-lymphocyte responses and control viral replication after pathogenic SIV infection. J Virol 74, 7485–7495.[CrossRef]
    [Google Scholar]
  9. Haslett, P. A. J., Nixon, D. F., Shen, Z., Larsson, M., Cox, W. I., Manandhar, R., Donahoe, S. M. & Kaplan, G. ( 2000; ). Strong human immunodeficiency virus (HIV)-specific CD4+ T cell responses in a cohort of chronically infected patients are associated with interruptions in anti-HIV chemotherapy. J Infect Dis 181, 1264–1272.[CrossRef]
    [Google Scholar]
  10. Hazenberg, M. D., Otto, S. A., Cohen Stuart, J. W. T. & 11 other authors ( 2000; ). Increased cell division but not thymic dysfunction rapidly affects the T-cell receptor excision circle content of the naive T cell population in HIV-1 infection. Nat Med 6, 1036–1042.[CrossRef]
    [Google Scholar]
  11. Jin, X., Bauer, D. E., Tuttleton, S. E. & 11 other authors ( 1999; ). Dramatic rise in plasma viremia after CD8+ T cell depletion in simian immunodeficiency virus-infected macaques. J Exp Med 189, 991–998.[CrossRef]
    [Google Scholar]
  12. Kostrikis, L. G., Tyagi, S., Mhlanga, M. M., Ho, D. D. & Kramer, R. F. ( 1998; ). Spectral genotyping of human alleles. Science 279, 1228–1229.[CrossRef]
    [Google Scholar]
  13. Larsson, M., Jin, X. Ramratnam, B. & 8 other authors ( 1999; ). A recombinant vaccinia virus based ELISPOT assay detects high frequencies of Pol-specific CD8 T cells in HIV-1-positive individuals. AIDS 13, 767–777.[CrossRef]
    [Google Scholar]
  14. Lifson, J. D., Rossio, J. L., Piatak, M., Jr & 15 other authors ( 2001; ). Role of CD8+ lymphocytes in control of simian immunodeficiency virus infection and resistance to rechallenge after transient early antiretroviral treatment. J Virol 75, 10187–10199.[CrossRef]
    [Google Scholar]
  15. Mackall, C. L., Hakim, F. T. & Gress, R. E. ( 1997; ). Restoration of T-cell homeostasis after T-cell depletion. Semin Immunol 9, 339–346.[CrossRef]
    [Google Scholar]
  16. Mackay, G. A., Liu, Z., Singh, D. K. & 9 other authors ( 2004; ). Protection against late-onset AIDS in macaques prophylactically immunized with a live simian HIV vaccine was dependent on persistence of the vaccine virus. J Immunol 173, 4100–4107.[CrossRef]
    [Google Scholar]
  17. Madden, L. J., Zandonatti, M. A., Flynn, C. T., Taffe, M. A., Marcondes, M. C., Schmitz, J. E., Reimann, K. A., Henriksen, S. J. & Fox, H. S. ( 2004; ). CD8+ cell depletion amplifies the acute retroviral syndrome. J Neurovirol 10 (Suppl. 1), 58–66.[CrossRef]
    [Google Scholar]
  18. Metzner, K. J., Jin, X., Lee, F. V. & 8 other authors ( 2000; ). Effects of in vivo CD8+ T cell depletion on virus replication in rhesus macaques immunized with a live, attenuated simian immunodeficiency virus vaccine. J Exp Med 191, 1921–1931.[CrossRef]
    [Google Scholar]
  19. Montefiori, D. C., Robinson, W. E., Jr, Schuffman, S. S. & Mitchell, W. M. ( 1988; ). Evaluation of antiviral drugs and neutralizing antibodies to human immunodeficiency virus by a rapid and sensitive microtiter infection assay. J Clin Microbiol 26, 231–235.
    [Google Scholar]
  20. Montefiori, D. C., Baba, T. W., Li, A., Bilska, M. & Ruprecht, R. M. ( 1996; ). Neutralizing and infection-enhancing antibody responses do not correlate with the differential pathogenicity of SIVmac239delta3 in adult and infant rhesus monkeys. J Immunol 157, 5528–5535.
    [Google Scholar]
  21. Moretto, W. J., Drohan, L. A. & Nixon, D. F. ( 2000; ). Rapid quantification of SIV-specific CD8 T cell responses with recombinant vaccinia virus ELISPOT or cytokine flow cytometry. AIDS 14, 2625–2627.[CrossRef]
    [Google Scholar]
  22. Pantaleo, G. & Koup, R. A. ( 2004; ). Correlates of immune protection in HIV-1 infection: what we know, what we don't know, what we should know. Nat Med 10, 806–810.[CrossRef]
    [Google Scholar]
  23. Rasmussen, R. A., Hofmann-Lehmann, R., Li, P.-L. & 8 other authors ( 2002; ). Neutralizing antibodies as a potential secondary protective mechanism during chronic SHIV infection in CD8+ T-cell-depleted macaques. AIDS 16, 829–838.[CrossRef]
    [Google Scholar]
  24. Regier, D. A. & Desrosiers, R. C. ( 1990; ). The complete nucleotide sequence of a pathogenic molecular clone of simian immunodeficiency virus. AIDS Res Hum Retroviruses 6, 1221–1231.
    [Google Scholar]
  25. Schmitz, J. E., Kuroda, M. J., Santra, S. & 13 other authors ( 1999; ). Control of viremia in simian immunodeficiency virus infection by CD8+ lymphocytes. Science 283, 857–860.[CrossRef]
    [Google Scholar]
  26. Schmitz, J. E., Kuroda, M. J., Santra, S. & 14 other authors ( 2003; ). Effect of humoral immune responses on controlling viremia during primary infection of rhesus monkeys with simian immunodeficiency virus. J Virol 77, 2165–2173.[CrossRef]
    [Google Scholar]
  27. Sharpe, S. A., Cope, A., Dowall, S. & 8 other authors ( 2004; ). Macaques infected long-term with attenuated simian immunodeficiency virus (SIVmac) remain resistant to wild-type challenge, despite declining cytotoxic T lymphocyte responses to an immunodominant epitope. J Gen Virol 85, 2591–2602.[CrossRef]
    [Google Scholar]
  28. Sodora, D. L., Douek, D. C., Silvestri, G. & 8 other authors ( 2000; ). Quantification of thymic function by measuring T cell receptor excision circles within peripheral blood and lymphoid tissues in monkeys. Eur J Immunol 30, 1145–1153.[CrossRef]
    [Google Scholar]
  29. Trkola, A., Kuster, H., Leemann, C. & 10 other authors ( 2004; ). Humoral immunity to HIV-1: kinetics of antibody responses in chronic infection reflects capacity of immune system to improve viral set point. Blood 104, 1784–1792.[CrossRef]
    [Google Scholar]
  30. Van Rompay, K. K. A., Cherrington, J. M., Marthas, M. L. & 8 other authors ( 1996; ). 9-[2-(Phosphonomethoxy)propyl]adenine therapy of established simian immunodeficiency virus infection in infant rhesus macaques. Antimicrob Agents Chemother 40, 2586–2591.
    [Google Scholar]
  31. Van Rompay, K. K. A., Cherrington, J. M., Marthas, M. L., Lamy, P. D., Dailey, P. J., Canfield, D. R., Tarara, R. P., Bischofberger, N. & Pedersen, N. C. ( 1999; ). 9-[2-(Phosphonomethoxy)propyl]adenine (PMPA) therapy prolongs survival of infant macaques inoculated with simian immunodeficiency virus with reduced susceptibility to PMPA. Antimicrob Agents Chemother 43, 802–812.
    [Google Scholar]
  32. Van Rompay, K. K. A., Miller, M. D., Marthas, M. L. & 8 other authors ( 2000; ). Prophylactic and therapeutic benefits of short-term 9-[2-(R)-(phosphonomethoxy)propyl]adenine (PMPA) administration to newborn macaques following oral inoculation with simian immunodeficiency virus with reduced susceptibility to PMPA. J Virol 74, 1767–1774.[CrossRef]
    [Google Scholar]
  33. Van Rompay, K. K. A., Singh, R. P., Pahar, B., Sodora, D. L., Wingfield, C., Lawson, J. R., Marthas, M. L. & Bischofberger, N. ( 2004; ). CD8+-cell-mediated suppression of virulent simian immunodeficiency virus during tenofovir treatment. J Virol 78, 5324–5337.[CrossRef]
    [Google Scholar]
  34. Whitney, J. B. & Ruprecht, R. M. ( 2004; ). Live attenuated HIV vaccines: pitfalls and prospects. Curr Opin Infect Dis 17, 17–26.[CrossRef]
    [Google Scholar]
  35. Zhang, L., Lewin, S. R., Markowitz, M. & 16 other authors ( 1999; ). Measuring recent thymic emigrants in blood of normal and HIV-1-infected individuals before and after effective therapy. J Exp Med 190, 725–732.[CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.81206-0
Loading
/content/journal/jgv/10.1099/vir.0.81206-0
Loading

Data & Media loading...

Supplements

vol. , part 12, pp. 3375 – 3384

Quantification of SIV T-cell receptor excision circles (TREC) by real-time PCR and FACS analysis of cell subsets

Assessment of thymic output and peripheral CD8 T-cell proliferation following CD8 T-cell depletion.

[ Single PDF file] (409 KB)



PDF

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error