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Journal of Virology, January 2003, p. 291-300, Vol. 77, No. 1
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.1.291-300.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Ontogeny and Specificities of Mucosal and Blood Human Immunodeficiency Virus Type 1-Specific CD8+ Cytotoxic T Lymphocytes

L. Musey,1,{dagger} Y. Ding,1 J. Cao,1 J. Lee,1 C. Galloway,1 A. Yuen,2 K. R. Jerome,2,3 and M. J. McElrath1,2,3*

Departments of Medicine,1 Laboratory Medicine, University of Washington,3 Program in Infectious Diseases, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 981092

Received 26 June 2002/ Accepted 16 September 2002

Induction of adaptive immunity to human immunodeficiency virus type 1 (HIV-1) at the mucosal site of transmission is poorly understood but crucial in devising strategies to control and prevent infection. To gain further understanding of HIV-1-specific T-cell mucosal immunity, we established HIV-1-specific CD8+ cytotoxic T-lymphocyte (CTL) cell lines and clones from the blood, cervix, rectum, and semen of 12 HIV-1-infected individuals and compared their specificities, cytolytic function, and T-cell receptor (TCR) clonotypes. Blood and mucosal CD8+ CTL had common HIV-1 epitope specificities and major histocompatibility complex restriction patterns. Moreover, both systemic and mucosal CTL lysed targets with similar efficiency, primarily through the perforin-dependent pathway in in vitro studies. Sequence analysis of the TCRß VDJ region revealed in some cases identical HIV-1-specific CTL clones in different compartments in the same HIV-1-infected individual. These results clearly establish that a subset of blood and mucosal HIV-1-specific CTL can have a common origin and can traffic between anatomically distinct compartments. Thus, these effectors can provide immune surveillance at the mucosa, where rapid responses are needed to contain HIV-1 infection.

* Corresponding author. Mailing address: Program in Infectious Diseases, Fred Hutchinson Cancer Research Center, Room D3-100, 1100 Fairview Ave. North, Seattle, WA 98109. Phone: (206) 667-6704. Fax: (206) 667-4411. E-mail: kd{at}u.washington.edu.

{dagger} Present address: Merck Research Laboratories, Blue Bell, PA 19422.

Journal of Virology, January 2003, p. 291-300, Vol. 77, No. 1
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.1.291-300.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.





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