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Antiviral effect and ex vivo CD4<sup>+</sup> T cell proliferation in HIV-positive patients as a result of CD28 costimulation

Levine, BL and Mosca, JD and Riley, JL and Carroll, RG and Vahey, MT and Jagodzinski, LL and Wagner, KF and Mayers, DL and Burke, DS and Weislow, OS and St. Louis, DC and June, CH (1996) Antiviral effect and ex vivo CD4<sup>+</sup> T cell proliferation in HIV-positive patients as a result of CD28 costimulation. Science, 272 (5270). 1939 - 1943. ISSN 0036-8075

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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 vital 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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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Levine, BL
Mosca, JD
Riley, JL
Carroll, RG
Vahey, MT
Jagodzinski, LL
Wagner, KF
Mayers, DL
Burke, DSdonburke@pitt.eduDONBURKE
Weislow, OS
St. Louis, DC
June, CH
Centers: Other Centers, Institutes, Offices, or Units > Center for Vaccine Research
Date: 28 June 1996
Date Type: Publication
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Journal or Publication Title: Science
Volume: 272
Number: 5270
Page Range: 1939 - 1943
DOI or Unique Handle: 10.1126/science.272.5270.1939
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Epidemiology
Refereed: Yes
ISSN: 0036-8075
Date Deposited: 08 May 2015 15:08
Last Modified: 22 Jun 2021 13:56


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