Stimulation of a human T-cell clone with anti-CD3 or tumor necrosis factor induces NF-kappa B translocation but not human immunodeficiency virus 1 enhancer-dependent transcription.

Abstract

The expression of transiently transfected expression vectors under the control of the long terminal repeat (LTR) of the human immunodeficiency virus (HIV) or its enhancer sequence and the translocation of the HIV enhancerbinding protein NF-KB were analyzed in two human T-cell clones stimulated through their T-cell receptor complex or by tumor necrosis factor or phorbol 12-myristate 13-acetate. We found a dissociation of NF-KB translocation from transactivation of either the HIV LTR or the HIV enhancer. Interleukin 2 induced proliferation but not NF-cB translocation or LTR transactivation. Phorbol ester or specific antigen recognition induced HIV LTR transactivation, whereas stimulation with tumor necrosis factor or antibody to CD3 did not. The two latter signals were nevertheless able to induce NF-KB translocation with a pattern in the band-shift assay indistinguishable from that observed using phorbol ester. Our rmding that induction of NF-cB by tumor necrosis factor or antibody to CD3 is not sufficient to induce HIV enhancer-dependent transcription in cloned T cells contrasts with results obtained in most lymphoblastoid T-cell lines and indicates that normal T lymphocytes differ from tumoral T cells in terms of requirements for HIV LTR activation. Furthermore, our results suggest that events linked to T-cell activation, in addition to NF-KB translocation per se, induce functional interactions of the NF-KB complex with the HIV enhancer.

Preferential replication of HIV-1 in the CD45RO memory cell subset of primary CD4 lymphocytes in vitro.

“…It is known that the phosphatase activity of CD45 is essential for activation of CD4-associated p56/lck during triggering of the TCR/CD3 signaling cascade (59). The results from our study, as well as the findings with HIV-infected subjects (35,53,54,57), indicate that cell proliferation per se is less critical for support of HIV growth than is the specific, cell activation pathway engaged. This premise is bolstered by work from another laboratory, demonstrating that RA cells support minimal HIV replication, when induced to proliferate using a cytokine stimulus that maintains their RA phenotype (60).…”

“…Although the best inducers of in vitro HIV replication, such as lectins and immobilized antibodies to CD3, share strong mitogenic properties, the ability of a stimulus to produce cell proliferation has not always correlated directly with its capacity to induce virus replication in cells from HIV patients (28,35,(53)(54)(55). Most recently, data generated from patient samples have demonstrated that in vitro induction with immobilized anti-CD3 plus anti-CD28 results in a loss of HIV-producing cells and a preferential survival of uninfected CD4 cells during long-term culture (51).…”

A novel NF-kappa B complex containing p65 homodimers: implications for transcriptional control at the level of subunit dimerization.

“…This specific inductive event is initiated upon cellular stimulation with a variety of soluble mediators, including T-cell receptor ligands (22,29,33,34), interleukin-1 (52,63), interleukin-2 (3), tumor necrosis factor alpha (40,52), and phorbol esters (5,12,62). Prior studies have revealed that the major inducible form of NF-KB corresponds to a heterodimeric complex composed of 65-kDa (p65) and 50-kDa (p50) subunits (6).…”

Differential requirements for HIV-1 replication in naive and memory CD4 T cells from asymptomatic HIV-1 seropositive carriers and AIDS patients

“…In this respect, recent work [24] reported an anti-CD3-induced sequence-specific DNA-binding protein which recognizes an upstream regulatory element on HIV-2 long terminal repeat (LTR). In addition, human CD4 T cell clones have been reported to induce HIVenhancer-dependent transcription after PMA stimulation, but not after rTNF-a and anti-CD3 treatment, suggesting different requirements for NFkB-mediated HIV replication between tumoral T cell lines and human CD4 T cell clones [12]. Moreover, it cannot be excluded that requirements for freshly purified CD4 T ceil subsets from HIV-1 -infected patients differ from those of lymphoblastoid T cell lines and human CD4 T cell clones.…”

“…II has been well established that phorbol esters and rTNI--a efficiently induce HIV-1 replication in several 'in vitro systems" [12][13][14][15][16][17].…”