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Antiviral Effect and Ex Vivo CD4 + T Cell Proliferation in HIV-Positive Patients as a Result of CD28 Costimulation
Abstract
Because stimulation of CD4 + lymphocytes leads to activation of human immunodeficiency virus-type 1 (HIV-1) replication, viral spread, and cell death, adoptive CD4 + T cell therapy has not been possible. When antigen and CD28 receptors on cultured T cells were stimulated by monoclonal antibodies (mAbs) to CD3 and CD28 that had been immobilized, there was an increase in the number of polyclonal CD4 + T cells from HIV-infected donors. Activated cells predominantly secreted cytokines associated with T helper cell type 1 function. The HIV-1 viral load declined in the absence of antiretroviral agents. Moreover, CD28 stimulation of CD4 + T cells from uninfected donors rendered these cells highly resistant to HIV-1 infection. Immobilization of CD28 mAb was crucial to the development of HIV resistance, as cells stimulated with soluble CD28 mAb were highly susceptible to HIV infection. The CD28-mediated antiviral effect occurred early in the viral life cycle, before HIV-1 DNA integration. These data may facilitate immune reconstitution and gene therapy approaches in persons with HIV infection.
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Cited by
The HIV coreceptors CXCR4 and CCR5 are differentially expressed and regulated on human T lymphocytes
Bleul, C. C., Wu, L., Hoxie, J. A., Springer, T. A., & Mackay, C. R. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.5.1925 · Cited by 1,134
Mitsuyasu, R. T., Anton, P. A., Deeks, S. G., Scadden, D. T., Connick, E., Downs, M. T., Bakker, A., Roberts, M. R., June, C. H., Jalali, S., et al. (2000) · Blood · doi:10.1182/blood.v96.3.785 · Cited by 425
Self-citationEngineering HIV-resistant human CD4+ T cells with CXCR4-specific zinc-finger nucleases
Wilen, C. B., Wang, J., Tilton, J. C., Miller, J. C., Kim, K. A., Rebar, E. J., Sherrill-Mix, S. A., Patro, S. C., Secreto, A. J., Jordan, A. P. O., et al. (2011) · PLoS Pathogens · doi:10.1371/journal.ppat.1002020 · Cited by 142
Maier, D. A., Brennan, A. L., Jiang, S., Binder-Scholl, G. K., Lee, G., Plesa, G., Zheng, Z., Cotte, J., Carpenito, C., Wood, T., et al. (2013) · Human Gene Therapy · doi:10.1089/hum.2012.172 · Cited by 126
Self-citationCasati, A., Varghaei-Nahvi, A., Feldman, S. A., Assenmacher, M., Rosenberg, S. A., Dudley, M. E., & Scheffold, A. (2013) · Cancer Immunology, Immunotherapy · doi:10.1007/s00262-013-1459-x · Cited by 73
Metadata
- Authors
- Levine, B. L., Mosca, J. D., Riley, J. L., Carroll, R. G., Vahey, M. T., Jagodzinski, L. L., Wagner, K. F., Mayers, D. L., Burke, D. S., Weislow, O. S., St. Louis, D. C., & June, C. H.
- Venue
- Science
- Published
- 1996-06-28
- Volume
- 272
- Issue
- 5270
- Pages
- 1939-1943
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2009014910
- Cited by
- 220
- References
- 0
- FWCI
- 6.71
- Type
- journal article
- Language
- en
- Open access
- closed
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- CoChat. (2026). Citation check: Antiviral Effect and Ex Vivo CD4 + T Cell Proliferation in HIV-Positive Patients as a Result of CD28 Costimulation. https://app.cochat.ai/papers/10.1126/science.272.5270.1939
- The paper
- Levine, B. L., Mosca, J. D., Riley, J. L., Carroll, R. G., Vahey, M. T., Jagodzinski, L. L., Wagner, K. F., Mayers, D. L., Burke, D. S., Weislow, O. S., St. Louis, D. C., & June, C. H. (1996). Antiviral Effect and Ex Vivo CD4 + T Cell Proliferation in HIV-Positive Patients as a Result of CD28 Costimulation. Science. https://doi.org/10.1126/science.272.5270.1939
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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