Elicitation of simian immunodeficiency virus-specific cytotoxic T lymphocytes in mucosal compartments of rhesus monkeys by systemic vaccination

Jamal Baig, Daniel B. Levy, Paul F. McKay, Joern E. Schmitz, Sampa Santra, Ramu A. Subbramanian, Marcelo J. Kuroda, Michelle A. Lifton, Darci A. Gorgone, Linda S. Wyatt, Bernard Moss, Yue Huang, Bimal K. Chakrabarti, Ling Xu, Wing Pui Kong, Zhi Yong Yang, John R. Mascola, Gary J. Nabel, Angela Carville, Andrew A. LacknerRonald S. Veazey, Norman L. Letvin

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

Since most human immunodeficiency virus (HIV) infections are initiated following mucosal exposure to the virus, the anatomic containment or abortion of an HIV infection is likely to require vaccine-elicited cellular immune responses in those mucosal sites. Studying vaccine-elicited mucosal immune responses has been problematic because of the difficulties associated with sampling T lymphocytes from those anatomic compartments. In the present study, we demonstrate that mucosal cytotoxic T lymphocytes (CTL) specific for simian immunodeficiency virus (SIV) and simian HIV can be reproducibly sampled from intestinal mucosal tissue of rhesus monkeys obtained under endoscopic guidance. These lymphocytes recognize peptide-major histocompatibility complex class I complexes and express gamma interferon on exposure to peptide antigen. Interestingly, systemic immunization of monkeys with plasmid DNA immunogens followed by live recombinant attenuated poxviruses or adenoviruses with genes deleted elicits high-frequency SIV-specific CTL responses in these mucosal tissues. These studies therefore suggest that systemic delivery of potent HIV immunogens may suffice to elicit substantial mucosal CTL responses.

Original languageEnglish (US)
Pages (from-to)11484-11490
Number of pages7
JournalJournal of Virology
Volume76
Issue number22
DOIs
StatePublished - 2002
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

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