Elicitation of simian immunodeficiency virus-specific cytotoxic T lymphocytes in mucosal compartments of rhesus monkeys by systemic vaccination.
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.
Baig
Jamal
J
Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
Levy
Daniel B
DB
McKay
Paul F
PF
Schmitz
Joern E
JE
Santra
Sampa
S
Subbramanian
Ramu A
RA
Kuroda
Marcelo J
MJ
Lifton
Michelle A
MA
Gorgone
Darci A
DA
Wyatt
Linda S
LS
Moss
Bernard
B
Huang
Yue
Y
Chakrabarti
Bimal K
BK
Xu
Ling
L
Kong
Wing-Pui
WP
Yang
Zhi-Yong
ZY
Mascola
John R
JR
Nabel
Gary J
GJ
Carville
Angela
A
Lackner
Andrew A
AA
Veazey
Ronald S
RS
Letvin
Norman L
NL
D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D003106:Colon / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology*; D007583:Jejunum / Q000276:immunology; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014611:Vaccination; D019444:Vaccines, DNA
D016915:AIDS Vaccines; D019444:Vaccines, DNA