Suppression of HIV replication by lymphoid tissue CD8+ cells correlates with the clinical state of HIV-infected individuals

David J. Blackbourn*, Carl E. Mackewicz, Edward Barker, Thomas K. Hunt, Brian Herndier, Ashley T. Haase, Jay A. Levy

*Corresponding author for this work

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70 Citations (Scopus)


Lymphoid tissues from asymptomatic HIV-infected individuals, as compared with symptomatic HIV-infected subjects, show limited histopathological changes and lower levels of HIV expression. In this report we correlate the control of HIV replication in lymph nodes to the non-cytolytic anti-HIV activity of lymphoid tissue CD8+ cells. Five subjects at different stages of HIV-related disease were studied and the ability of their CD8+ cells, isolated from both lymphoid tissue and peripheral blood, to inhibit HIV replication was compared. CD8+ cells from lymphoid tissue and peripheral blood of two HIV-infected long-term survivors suppressed HIV replication at a low CD8+:CD4+ cell ratio of 0.1. The CD8+ cells from the lymphoid tissue of a third asymptomatic subject suppressed HIV replication at a CD8+:CD4+ cell ratio of 0.25; the subject's peripheral blood CD8+ cells showed this antiviral response at a lower ratio of 0.05. The lymphoid tissue CD8+ cells from two AIDS patients were nut able to suppress HIV replication, and the peripheral blood CD8+ cells of only one of them suppressed HIV replication. The plasma viremia, cellular HIV load as well as the extent of pathology and virus expression in the lymphoid tissue of the two long-term survivors, were reduced compared with these parameters in the three other subjects. The data suggest that the extent of anti-HIV activity by CD8+ cells from lymphoid tissue relative to peripheral blood correlates best with the clinical state measured by lymphoid tissue pathology and HIV burden in lymphoid tissues and blood. The results add further emphasis to the importance of this cellular immune response in controlling HIV pathogenesis.

Original languageEnglish
Pages (from-to)13125-13130
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number23
Publication statusPublished - 12 Nov 1996

Bibliographical note

We thank Bineetha Ramachandran, Roland Orque, and Tesi Low for technical assistance, Sue Fujimura for flow cytometry studies, and Kris Gebhard for in situ hybridization studies. The tonsilectomy was performed by Dr. K. H. Wu (Department of Head and Neck Surgery, Kaiser Hospital, San Francisco). Christine Beglinger helped in the preparation of this manuscript. D.J.B. was supported in part by the University of California Universitywide AIDS Research Program (Grant F94-SF-008).


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