This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mackewicz, C. E. Articles by Levy, J. A. Search for Related Content PubMed PubMed Citation Articles by Mackewicz, C. E. Articles by Levy, J. A.

Journal of Virology, December 1998, p. 10165-10170, Vol. 72, No. 12
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

HLA Compatibility Requirements for CD8⁺-T-Cell-Mediated Suppression of Human Immunodeficiency Virus Replication

Carl E. Mackewicz,¹ Marvin R. Garovoy,^2, and Jay A. Levy^1,*

Department of Medicine¹ and Immunogenetics and Transplantation Laboratory, Department of Surgery,² School of Medicine, University of California, San Francisco, San Francisco, California 94143-1270

Received 14 July 1998/Accepted 1 September 1998

CD8⁺ T cells from human immunodeficiency virus (HIV)-infected individuals can suppress HIV replication in cultured CD4⁺ cells by a noncytotoxic mechanism. Efficient suppression of HIV replication (>90% reduction) does not require HLA class I or class II histocompatibility between the effector CD8⁺ T cells and the infected target CD4⁺ T cells. However, maximal control of HIV production occurs when the CD8⁺ effector cells and CD4⁺ target cells are syngeneic. In some cases, more than 20-fold fewer syngeneic CD8⁺ T cells were required to achieve the same degree of HIV inhibition as HLA-mismatched CD8⁺ T cells. The increased antiviral activity seen in the syngeneic setting did not map exclusively to either the HLA class I or class II locus. These findings suggest that genetic compatibility (potentially, but not necessarily, at the HLA class I and class II loci) regulates CD8⁺ T-cell noncytotoxic antiviral activity against infected CD4⁺ T cells.

---

^* Corresponding author. Mailing address: Department of Medicine, School of Medicine, University of California, San Francisco, San Francisco, CA 94143-1270. Phone: (415) 476-4071. Fax: (415) 476-8365. E-mail: jalevy{at}itsa.ucsf.edu.

Present address: Xoma Corporation, Berkeley, CA 94170.

---

Journal of Virology, December 1998, p. 10165-10170, Vol. 72, No. 12
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

This article has been cited by other articles:

• Diaz, L. S., Foster, H., Stone, M. R., Fujimura, S., Relman, D. A., Levy, J. A. (2005). VCAM-1 Expression on CD8+ Cells Correlates with Enhanced Anti-HIV Suppressing Activity. J. Immunol. 174: 1574-1579 [Abstract] [Full Text]  
• Mackewicz, C. E., Craik, C. S., Levy, J. A. (2003). The CD8+ cell noncytotoxic anti-HIV response can be blocked by protease inhibitors. Proc. Natl. Acad. Sci. USA 100: 3433-3438 [Abstract] [Full Text]  
• Chun, T.-W., Justement, J. S., Moir, S., Hallahan, C. W., Ehler, L. A., Liu, S., McLaughlin, M., Dybul, M., Mican, J. M., Fauci, A. S. (2001). Suppression of HIV replication in the resting CD4+ T cell reservoir by autologous CD8+ T cells: Implications for the development of therapeutic strategies. Proc. Natl. Acad. Sci. USA 98: 253-258 [Abstract] [Full Text]  
• Salerno-Gonçalves, R., Lu, W., Andrieu, J.-M. (2000). Quantitative Analysis of the Antiviral Activity of CD8+ T Cells from Human Immunodeficiency Virus-Positive Asymptomatic Patients with Different Rates of CD4+ T-Cell Decrease. J. Virol. 74: 6648-6651 [Abstract] [Full Text]  
• Tomaras, G. D., Lacey, S. F., McDanal, C. B., Ferrari, G., Weinhold, K. J., Greenberg, M. L. (2000). CD8+ T cell-mediated suppressive activity inhibits HIV-1 after virus entry with kinetics indicating effects on virus gene expression. Proc. Natl. Acad. Sci. USA 97: 3503-3508 [Abstract] [Full Text]