       Document 0597
 DOCN  M9630597
 TI    Costimulation of CD4+ T cells via CD28 modulates human immunodeficiency
       virus type 1 infection and replication in vitro.
 DT    9603
 AU    Smithgall MD; Wong JG; Linsley PS; Haffar OK; Bristol-Myers Squibb
       Pharmaceutical Research Institute, Seattle,; Washington 98121, USA.
 SO    AIDS Res Hum Retroviruses. 1995 Aug;11(8):885-92. Unique Identifier :
       AIDSLINE MED/96020089
 AB    Stimulation of human immunodeficiency virus type 1 (HIV-1)-infected
       donor peripheral blood mononuclear cells (PBMCs) via the TCR-CD3 complex
       induces HIV-1 production in vitro (Zarling JM, et al.: Nature [London]
       1990;347:92; Haffar OK, et al.: J Virol 1992;66:4279; Moran PM, et al.:
       AIDS Res Hum Retroviruses 1993;9:455). However, in addition to the
       primary stimulatory signal delivered through the TCR-CD3 complex,
       optimal T cell activation requires secondary or costimulatory signals
       delivered via various T cell accessory proteins (Alton A, et al.: Adv
       Immunol 1990;48:227). In this article we explore the role of
       costimulation of T cells via CD28 in HIV-1 replication. Ligation of CD28
       with either a CD28-specific MAb or by coculture of PBMCs with Chinese
       hamster ovary (CHO) cell lines stably expressing either of the CD28
       counterreceptors, B7-1 (CD80) or B7-2 (CD86), concomitant with
       stimulation via CD3, results in increased virus replication compared to
       stimulation via CD3 alone. CD28 ligation also augments de novo infection
       of CD3-stimulated seronegative donor PBMCs with cell-free virus.
       Increased virus replication following CD28 ligation is not solely
       attributed to increased levels of endogenous IL-2, because addition of
       an anti-IL-2-neutralizing antibody only partially inhibits the response.
       In contrast, interfering with the interaction between CD28 and its
       counterreceptors on antigen-presenting cells (APCs) using CTLA4Ig
       effectively inhibits virus replication. At high concentrations CTLA4Ig
       also reduces cell proliferation. These in vitro results suggest that
       CD28 plays a central role in HIV-1 replication and that interfering with
       the CD28 costimulatory pathway may modify the course of HIV-1 infection.
 DE    Animal  Antigens, CD28/*PHYSIOLOGY  Antigens, CD3/PHYSIOLOGY  Coculture
       CD4-Positive T-Lymphocytes/PHYSIOLOGY/*VIROLOGY  CHO Cells  Hamsters
       Human  HIV Infections/*VIROLOGY  HIV-1/*PHYSIOLOGY  Signal Transduction
       Virus Replication/*PHYSIOLOGY  JOURNAL ARTICLE

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

