Induction of mucosal homing virus-specific CD8(+) T lymphocytes by attenuated simian immunodeficiency virus.
Induction of virus-specific T-cell responses in mucosal as well as systemic compartments of the immune system is likely to be a critical feature of an effective AIDS vaccine. We investigated whether virus-specific CD8(+) lymphocytes induced in rhesus macaques by immunization with attenuated simian immunodeficiency virus (SIV), an approach that is highly effective in eliciting protection against mucosal challenge, express the mucosa-homing receptor alpha4beta7 and traffic to the intestinal mucosa. SIV-specific CD8(+) T cells expressing alpha4beta7 were detected in peripheral blood and intestine of macaques infected with attenuated SIV. In contrast, virus-specific T cells in blood of animals immunized cutaneously by a combined DNA-modified vaccinia virus Ankara regimen did not express alpha4beta7. These results demonstrate the selective induction of SIV-specific CD8(+) T lymphocytes expressing alpha4beta7 by a vaccine approach that replicates in mucosal tissue and suggest that induction of virus-specific lymphocytes that are able to home to mucosal sites may be an important characteristic of a successful AIDS vaccine.
Cromwell
M A
MA
Divisions of Immunology, New England Regional Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772, USA.
Veazey
R S
RS
Altman
J D
JD
Mansfield
K G
KG
Glickman
R
R
Allen
T M
TM
Watkins
D I
DI
Lackner
A A
AA
Johnson
R P
RP
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000494:pharmacology; D007275:Injections, Intravenous; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology*; D008253:Macaca mulatta; D016201:Receptors, Lymphocyte Homing / Q000276:immunology*; D018449:SAIDS Vaccines / Q000276:immunology* / Q000494:pharmacology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014613:Vaccines, Attenuated / Q000276:immunology* / Q000494:pharmacology; D019444:Vaccines, DNA / Q000494:pharmacology; D014616:Vaccinia virus / Q000276:immunology
D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; C110764:Mamu-A 01 antigen; D016201:Receptors, Lymphocyte Homing; D018449:SAIDS Vaccines; D014613:Vaccines, Attenuated; D019444:Vaccines, DNA