Document 3246
 DOCN  M94A3246
 TI    HIV-1 infection of T cells in vitro is modulated by costimulation via
       CD28.
 DT    9412
 AU    Haffar OK; Smithgall M; Wong J; Linsley P; Bristol-Myers Squibb
       Pharmaceutical Research Institute, Seattle,; Washington 98121.
 SO    Int Conf AIDS. 1994 Aug 7-12;10(1):12 (abstract no. 022A). Unique
       Identifier : AIDSLINE ICA10/94369329
 AB    OBJECTIVE: We wanted to study the role of the T cell accessory molecule
       CD28 in the life cycle of HIV-1. METHODS: Peripheral blood mononuclear
       cells were isolated from blood of HIV-1 infected and uninfected donors,
       depleted of CD8+ T cells, and activated with a soluble anti-CD3 mAb
       alone or in combination with a anti-CD28 mAb. T cell activation was
       evaluated by measuring IL-2 production and proliferation. HIV-1 p24
       protein levels in the culture media and levels of HIV-1 proviral DNA in
       cells were used as an indices of virus production and spread. To
       abrogate the co-stimulation via CD28 we used CTLA4Ig, the soluble form
       of the CD28 homologue CTLA4, which binds with high avidity to both B7-1
       and B7-2 on antigen presenting cells. The role of CD28 costimulation on
       de novo infection of CD4+ cells with HIV-1 was addressed using the LAI
       isolate. RESULTS: Co-stimulation of HIV-1 infected PBMC with soluble
       anti-CD3 and anti-CD28 mAbs augmented virus production compared to
       stimulation with soluble anti-CD3 mAb alone. The effect of CD28
       stimulation was confirmed by coculture of the infected PBMC with a CHO
       cell line stably expressing the CD28 counter receptor B7-1. Increased
       virus production following engagement of CD28 could not be attributed
       solely to stimulation of IL-2 production since addition of an IL-2
       neutralizing mAb only partially inhibited the response. At high
       concentrations CTLA4Ig inhibited IL-2 production, proliferation, and
       virus production, while at low concentrations it selectively inhibited
       de novo infection and virus replication. DISCUSSION AND CONCLUSIONS:
       CD28-B7-1 association plays an integral role in the induction and spread
       of HIV-1 in vitro. These results suggest that abrogating this
       association with molecules such as CTLA4Ig may be therapeutically
       beneficial.
 DE    Antigens, CD28/*IMMUNOLOGY  Antigens, CD3/IMMUNOLOGY  Human  HIV Core
       Protein p24/ISOLATION & PURIF  HIV-1/*IMMUNOLOGY
       Interleukin-2/BIOSYNTHESIS  Lymphocyte Transformation  T-Lymphocyte
       Subsets/*MICROBIOLOGY  MEETING ABSTRACT

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).