Publication Date:
1996-06-28
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉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 -- AI29331/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 1996 Jun 28;272(5270):1939-43.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Naval Medical Research Institute, Bethesda, Maryland 20889, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8658167" target="_blank"〉PubMed〈/a〉
Keywords:
Antibodies, Monoclonal/immunology
;
Antigens, CD28/*immunology
;
Antigens, CD3/immunology
;
CD4 Lymphocyte Count
;
CD4-Positive T-Lymphocytes/cytology/*immunology/*virology
;
Cell Division
;
Cells, Cultured
;
Chemokines/metabolism
;
Cytokines/metabolism
;
HIV Infections/immunology/*virology
;
HIV-1/immunology/*physiology
;
Humans
;
Interleukin-2/pharmacology
;
*Lymphocyte Activation
;
Phytohemagglutinins/pharmacology
;
Virus Integration
;
Virus Replication
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
