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Science 28 June 1996:
Vol. 272. no. 5270, pp. 1939 - 1943
DOI: 10.1126/science.272.5270.1939
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Reports

Antiviral Effect and Ex Vivo CD4+ T Cell Proliferation in HIV-Positive Patients as a Result of CD28 Costimulation

Bruce L. Levine, Joseph D. Mosca, James L. Riley, Richard G. Carroll, Maryanne T. Vahey, Linda L. Jagodzinski, Kenneth F. Wagner, Douglas L. Mayers, Donald S. Burke, Owen S. Weislow, Daniel C. St. Louis, Carl H. June *

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.

B. L. Levine and C. H. June, Naval Medical Research Institute, Bethesda, MD 20889, USA.
J. D. Mosca, R. G. Carroll, L. L. Jagodzinski, K. F. Wagner, D. C. St. Louis, Henry M. Jackson Foundation for the Advancement of Military Medicine, Rockville, MD 20850, USA.
J. L. Riley, M. T. Vahey, D. S. Burke, Division of Retrovirology, Walter Reed Army Institute for Research, Rockville, MD 20850, USA.
D. L. Mayers, Naval Medical Research Institute, Bethesda, MD 20889, USA, and Division of Retrovirology, Walter Reed Army Institute for Research, Rockville, MD 20850, USA.
O. S. Weislow, Life Sciences Division, SRA Technologies, Rockville, MD 20850, USA.
* To whom correspondence should be addressed.


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Science. ISSN 0036-8075 (print), 1095-9203 (online)