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In vivo migration and function of transferred HIV-1-specific cytotoxic T cells

Nature Medicine volume 5, pages 34–41 (1999)Cite this article

Abstract

The persistence of HIV replication in infected individuals may reflect an inadequate host HIV-specific CD8 + cytotoxic T lymphocyte (CTL) response. The functional activity of HIV-specific CTLs and the ability of these effector cells to migrate in vivo to sites of infection was directly assessed by expanding autologous HIV-1 Gag-specific CD8 + CTL clones in vitro and adoptively transferring these CTLs to HIV-infected individuals. The transferred CTLs retained lytic function in vivo , accumulated adjacent to HIV-infected cells in lymph nodes and transiently reduced the levels of circulating productively infected CD4 + T cells. These results provide direct evidence that HIV-specific CTLs target sites of HIV replication and mediate antiviral activity, and indicate that the development of immunotherapeutic approaches to sustain a strong CTL response to HIV may be a useful adjunct to treatment of HIV infection.

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Figure 1
Figure 2: Analysis of presence and cytolytic activity in blood and lymph node of adoptively-transferred HIV-specific neo-modified CD8+ CTLs.
Figure 3: Antiviral activity of adoptively transferred HIV-specific CD8+ CTLs.
Figure 4: Migration of neo-modified CD8+ CTLs to lymph node and co-localization with HIV-infected cells.
Figure 5: Plasma HIV RNA levels during CTL therapy.

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Acknowledgements

We thank D. Spach (AIDS Clinical Trial Unit, University of Washington) for patient referral; K. Diem, M. Elliot, S. Friborg (Targeted Genetics), C. Hoffer, D. Kelly, C. B. Joiner, J. Joyce, V. Mosiman, D. Muthui, P.M. O'Hearn, E.L. Peterson, L. Wilson (Targeted Genetics) and B. Wood for technical assistance; B. Gilman and E. Gilman for their gift to the Program in Immunology; and Targeted Genetics for obtaining the IND for these studies, for providing the LN retroviral vector and for doing quality control testing. This study was supported by funds from the National Institutes of Health (AI36613 and AI41535 to S.B., P30 HD28834 and AI-27757 to D.L., AI30731 to S.R., P.D.G, and L.C.) and from the Pediatric AIDS Foundation, 77296-19—PF to D.L.

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Author notes

  1. Bruce K. Patterson, Daniel Jiyamapa and Philip D. Greenberg: Department of Obstetrics and Gynecology, Northwestern University Medical School, Chicago, Illinois 94404, USA S.J.B. and D.A.L. contributed equally to this work.

Authors and Affiliations

  1. Department of Laboratory Medicine, Box 356527, University of Washington, Seattle, 98101, Washington, USA

    Scott J. Brodie & Lawrence Corey

  2. Department of Pediatrics, Box 356527, University of Washington, Seattle, 98101, Washington, USA

    Deborah A. Lewinsohn

  3. Department of Urology, Box 356527, University of Washington, Seattle, 98101, Washington, USA

    John Krieger

  4. Department of Medicine, Box 356527, University of Washington, Seattle, 98101, Washington, USA

    Lawrence Corey, Philip D. Greenberg & Stanley R. Riddell

  5. Department of Immunology, Box 356527, University of Washington, Seattle, 98101, Washington, USA

    Philip D. Greenberg

  6. Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., D3-100, Seattle, 98109, Washington , USA

    Deborah A. Lewinsohn, Lawrence Corey, Philip D. Greenberg & Stanley R. Riddell

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Brodie, S., Lewinsohn, D., Patterson, B. et al. In vivo migration and function of transferred HIV-1-specific cytotoxic T cells. Nat Med 5, 34–41 (1999). https://doi.org/10.1038/4716

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