Md. Smithgall et al., COSTIMULATION OF CD4(-CELLS VIA CD28 MODULATES HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION AND REPLICATION IN-VITRO() T), AIDS research and human retroviruses, 11(8), 1995, pp. 885-892
Stimulation of human immunodeficiency virus type 1 (HIV-1)-infected do
nor 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, opti
mal T cell activation requires secondary or costimulatory signals deli
vered via various T cell accessory proteins (Alton A, et al.: Adv Immu
nol 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 eithe
r a CD28-specific MAb or by coculture of PBMCs with Chinese hamster ov
ary (CHO) cell lines stably expressing either of the CD28 counterrecep
tors, B7-1 (CD80) or B7-2 (CD86), concomitant with stimulation via CD3
, results in increased virus replication compared to stimulation via C
D3 alone, CD28 ligation also augments de novo infection of CD3-stimula
ted seronegative donor PBMCs with cell-free virus, Increased virus rep
lication following CD28 ligation is not solely attributed to increased
levels of endogenous IL-2, because addition of an anti-IL-2-neutraliz
ing antibody only partially inhibits the response, In contrast, interf
ering with the interaction between CD28 and its counterreceptors on an
tigen-presenting cells (APCs) using CTLA4Ig effectively inhibits virus
replication, At high concentrations CTLA4Ig also reduces cell prolife
ration, 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.