Anti-CD86 Anticorps [BU63] (FITC) (A85994)

Human immunodeficiency virus type 1 (HIV-1) carries virus-encoded and host-derived proteins. Recent advances in the functional characterization of host molecules inserted into mature virus particles have revealed that HIV-1 biology is influenced by the acquisition of host cell membrane components. The CD28/B7 receptor/ligand system is considered one of the fundamental elements of the normal immune response. Two major cell types that harbor HIV-1 in vivo, i.e., monocytes/macrophages and CD4+ T cells, express the costimulatory molecules CD80 (B7.1) and CD86 (B7.2). We investigated whether CD80 and CD86 are efficiently acquired by HIV-1, and if so, whether these host-encoded molecules can contribute to the virus life cycle. Here we provide the first evidence that the insertion of CD80 and CD86 into HIV-1 increases virus infectivity by facilitating the attachment and entry process due to interactions with their two natural ligands, CD28 and CTLA-4. Moreover, we demonstrate that NF-kappaB is induced by CD80- and CD86-bearing virions when they are combined with the engagement of the T-cell receptor/CD3 complex, an event that is inhibited upon surface expression of CTLA-4. Finally, both CD80 and CD86 were found to be efficiently incorporated into R5- and X4-tropic field strains of HIV-1 expanded in cytokine-treated macrophages. Thus, besides direct interactions between the virus envelope glycoproteins and cell surface constituents, such as CD4 and some specific chemokine coreceptors, HIV-1 may attach to target cells via interactions between cell-derived molecules incorporated into virions and their natural ligands. These findings support the theory that HIV-1-associated host proteins alter virus-host dynamics.

The development of cytotoxic CD4+ T lymphocytes that can kill target cells in a MHC class II-restricted manner was evaluated by comparing different APCs. B-lymphoblasts (B-LCL) pulsed with the superantigen staphylococcus enterotoxin B or allogeneic B-lymphoblasts induce CD4+ T cells without cytotoxic activity. In contrast, superantigen-pulsed, MHC class II+ T cell blasts or allogeneic T cell blasts preferentially induce the development of specific, MHC class II-restricted CD4+ cytotoxic effector cells. CD4+ T cell clones generated with T or B cell blasts as APCs (T- or B-APCs) differ in their cytolytic potential, but secrete a similar cytokine pattern. Our data implicate that activated T-APCs preferentially induce a cytotoxic, CD8+ and CD4+ T cell response. Because the density of CD80 expression is lower on activated T-APCs than on B-APCs, we studied the involvement of CD28 and CD80 adhesion molecules in the generation of CD4+ CTLs. Partial blockade of the CD80 molecule with a CTLA4-Ig fusion protein and with specific anti-CD80 mAbs on B-APCs enhanced the generation of CD4+ CTLs. Specific anti-CD86 mAbs, on the contrary, had no effect on the generation of CD4+ CTLs. In contrast, stimulation of CD28, the CD80 counter-receptor, with a cross-linked B7-Ig fusion protein or with an anti-CD28 mAb, inhibited the generation of CD4+ CTLs. Thus, a reduced interaction between CD80 and CD28 may be relevant for the induction of CD4+ CTLs. This shows a new and not yet described function of these adhesion molecules. This induction of a cytotoxic immune response by T cells as APCs may be relevant for the anticlonotypic regulation of T cells and for the depletion of CD4+ T cells in HIV infection.