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Journal of Virology, April 2005, p. 4289-4297, Vol. 79, No. 7
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.7.4289-4297.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Parallel Human Immunodeficiency Virus Type 1-Specific CD8+ T-Lymphocyte Responses in Blood and Mucosa during Chronic Infection

F. Javier Ibarrondo,1 Peter A. Anton,1 Marie Fuerst,1 Hwee L. Ng,1 Johnson T. Wong,2 Jose Matud,1 Julie Elliott,1 Roger Shih,1 Mary Ann Hausner,1 Charles Price,1 Lance E. Hultin,1 Patricia M. Hultin,1 Beth D. Jamieson,1 and Otto O. Yang1,3*

UCLA AIDS Institute and Department of Medicine, Geffen School of Medicine, UCLA Medical Center,1 Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, California,3 Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts2

Received 4 August 2004/ Accepted 27 October 2004

Gut-associated lymphoid tissue is the major reservoir of lymphocytes and human immunodeficiency virus type 1 (HIV-1) replication in vivo, yet little is known about HIV-1-specific CD8+ T-lymphocyte (CTL) responses in this compartment. Here we assessed the breadth and magnitude of HIV-1-specific CTL in the peripheral blood and sigmoid colon mucosa of infected subjects not on antiretroviral therapy by enzyme-linked immunospot analysis with 53 peptide pools spanning all viral proteins. Comparisons of blood and mucosal CTL revealed that the magnitude of pool-specific responses is correlated within each individual (mean r2 = 0.82 ± 0.04) and across all individuals (r2 = 0.75; P < 0.001). Overall, 85.1% of screened peptide pools yielded concordant negative or positive results between compartments. CTL targeting was also closely related between blood and mucosa, with Nef being the most highly targeted (mean of 2.4 spot-forming cells [SFC[/106 CD8+ T lymphocytes/amino acid [SFC/CD8/aa]), followed by Gag (1.5 SFC/CD8/aa). Finally, comparisons of peptide pool responses seen in both blood and mucosa (concordant positives) versus those seen only in one but not the other (discordant positives) showed that most discordant results were likely an artifact of responses being near the limit of detection. Overall, these results indicate that HIV-1-specific CTL responses in the blood mirror those seen in the mucosal compartment in natural chronic infection. For protective or immunotherapeutic vaccination, it will be important to determine whether immunity is elicited in the mucosa, which is a key site of initial infection and subsequent HIV-1 replication in vivo.

* Corresponding author. Mailing address: Division of Infectious Diseases, 37-121 CHS, UCLA Medical Center, 10833 LeConte Ave., Los Angeles, CA 90095. Phone: (310) 794-9491. Fax: (310) 825-3632. E-mail: oyang{at}mednet.ucla.edu.

Journal of Virology, April 2005, p. 4289-4297, Vol. 79, No. 7
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.7.4289-4297.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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