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Journal of Virology, September 2000, p. 8762-8766, Vol. 74, No. 18
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

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

Mandy A. Cromwell,1 Ronald S. Veazey,2 John D. Altman,3 Keith G. Mansfield,4 Rhona Glickman,1 Todd M. Allen,5 David I. Watkins,5 Andrew A. Lackner,2 and R. Paul Johnson1,6,*

Divisions of Immunology,1 Pathology,2 and Primate Medicine,4 New England Regional Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772; Emory Vaccine Center at Yerkes, Emory University School of Medicine, Atlanta, Georgia 303223; Wisconsin Regional Primate Research Center, University of Wisconsin, Madison, Wisconsin 537155; and Infectious Disease Unit and Partners AIDS Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 021156

Received 18 February 2000/Accepted 5 June 2000

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 alpha 4beta 7 and traffic to the intestinal mucosa. SIV-specific CD8+ T cells expressing alpha 4beta 7 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 alpha 4beta 7. These results demonstrate the selective induction of SIV-specific CD8+ T lymphocytes expressing alpha 4beta 7 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.


* Corresponding author. Mailing address: New England Regional Primate Research Center, Harvard Medical School, One Pine Hill Dr., P.O. Box 9102, Southborough, MA 01772-9102. Phone: (508) 624-8148. Fax: (508) 624-8172. E-mail: paul_johnson{at}hms.harvard.edu.


Journal of Virology, September 2000, p. 8762-8766, Vol. 74, No. 18
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.



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