Extralymphoid CD8 + T cells resident in tissue from simian immunodeficiency virus SIVmac239△nef-vaccinated macaques suppress SIVmac239 replication ex vivo

Justin M. Greene, Jennifer J. Lhost, Benjamin Burwitz, Melisa L. Budde, Caitlin E. Macnair, Madelyn K. Weiker, Emma Gostick, Thomas C. Friedrich, Karl W. Broman, David A. Price, Shelby L. O'Connor, David H. O'Connor

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Live-attenuated vaccination with simian immunodeficiency virus (SIV) SIVmac239△nef is the most successful vaccine product tested to date in macaques. However, the mechanisms that explain the efficacy of this vaccine remain largely unknown. We utilized an ex vivo viral suppression assay to assess the quality of the immune response in SIVmac239△nef-immunized animals. Using major histocompatibility complex-matched Mauritian cynomolgus macaques, we did not detect SIV-specific functional immune responses in the blood by gamma interferon (IFN-γ) enzyme-linked immunospot assay at select time points; however, we found that lung CD8 + T cells, unlike blood CD8 + T cells, effectively suppress virus replication by up to 80%. These results suggest that SIVmac239△nef may be an effective vaccine because it elicits functional immunity at mucosal sites. Moreover, these results underscore the limitations of relying on immunological measurements from peripheral blood lymphocytes in studies of protective immunity to HIV/SIV.

Original languageEnglish (US)
Pages (from-to)3362-3372
Number of pages11
JournalJournal of Virology
Volume84
Issue number7
DOIs
StatePublished - Apr 2010
Externally publishedYes

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Simian immunodeficiency virus
Simian Immunodeficiency Virus
Macaca
Vaccines
T-lymphocytes
vaccines
T-Lymphocytes
blood
immunity
immune response
Enzyme-Linked Immunospot Assay
Mucosal Immunity
Macaca fascicularis
major histocompatibility complex
assays
Virus Replication
virus replication
interferon-gamma
Major Histocompatibility Complex
Interferon-gamma

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Extralymphoid CD8 + T cells resident in tissue from simian immunodeficiency virus SIVmac239△nef-vaccinated macaques suppress SIVmac239 replication ex vivo. / Greene, Justin M.; Lhost, Jennifer J.; Burwitz, Benjamin; Budde, Melisa L.; Macnair, Caitlin E.; Weiker, Madelyn K.; Gostick, Emma; Friedrich, Thomas C.; Broman, Karl W.; Price, David A.; O'Connor, Shelby L.; O'Connor, David H.

In: Journal of Virology, Vol. 84, No. 7, 04.2010, p. 3362-3372.

Research output: Contribution to journalArticle

Greene, JM, Lhost, JJ, Burwitz, B, Budde, ML, Macnair, CE, Weiker, MK, Gostick, E, Friedrich, TC, Broman, KW, Price, DA, O'Connor, SL & O'Connor, DH 2010, 'Extralymphoid CD8 + T cells resident in tissue from simian immunodeficiency virus SIVmac239△nef-vaccinated macaques suppress SIVmac239 replication ex vivo', Journal of Virology, vol. 84, no. 7, pp. 3362-3372. https://doi.org/10.1128/JVI.02028-09
Greene, Justin M. ; Lhost, Jennifer J. ; Burwitz, Benjamin ; Budde, Melisa L. ; Macnair, Caitlin E. ; Weiker, Madelyn K. ; Gostick, Emma ; Friedrich, Thomas C. ; Broman, Karl W. ; Price, David A. ; O'Connor, Shelby L. ; O'Connor, David H. / Extralymphoid CD8 + T cells resident in tissue from simian immunodeficiency virus SIVmac239△nef-vaccinated macaques suppress SIVmac239 replication ex vivo. In: Journal of Virology. 2010 ; Vol. 84, No. 7. pp. 3362-3372.
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