Induction of Mucosal Homing Virus-Specific CD8 + T Lymphocytes by Attenuated Simian Immunodeficiency Virus

Author:

Cromwell Mandy A.1,Veazey Ronald S.2,Altman John D.3,Mansfield Keith G.4,Glickman Rhona1,Allen Todd M.5,Watkins David I.5,Lackner Andrew A.2,Johnson R. Paul16

Affiliation:

1. Divisions of Immunology,1

2. Pathology,2 and

3. Emory Vaccine Center at Yerkes, Emory University School of Medicine, Atlanta, Georgia 303223;

4. Primate Medicine,4 New England Regional Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772;

5. Wisconsin Regional Primate Research Center, University of Wisconsin, Madison, Wisconsin 537155; and

6. Infectious Disease Unit and Partners AIDS Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 021156

Abstract

ABSTRACT 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 α4β7 and traffic to the intestinal mucosa. SIV-specific CD8 + T cells expressing α4β7 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 α4β7. These results demonstrate the selective induction of SIV-specific CD8 + T lymphocytes expressing α4β7 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.

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

Reference31 articles.

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3. The imporance of local mucosal HIV-specific CD8+ cytotoxic T lymphocytes for resistance to mucosal viral transmission in mice and enhancement of resistance by local administration of IL-12;Belyakov I. M.;J. Clin. Investig.,1998

4. α4β7 integrin mediates lymphocyte binding to the mucosal vascular addressin MAdCAM-1;Berlin C.;Cell,1993

5. Butcher E. C. Lymphocyte homing and intestinal immunity Mucosal immunity. Ogra P. L. Mestecky J. Lamm M. E. Strober W. Bienenstock J. McGhee J. R. 1999 507 522 Academic Press San Diego Calif

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