Antigen presentation by naive macrophages, dendritic cells and B cells to primed T lymphocytes and their cytokine production following exposure to immunostimulating complexes

Abstract

SUMMARYInfluenza virus envelope proteins incorporated into immunostimulating complexes (iscoms) are taken up and processed by various kinds of antigen-presenting cells (APC), encompassing peritoneal cells (PEC), unfractionated splenocytes, splenic dendritic cells (DC) or B cells. The iscom-pulsed naive APC stimulated primed T cells to proliferate and produce cytokine in vitro. In contrast, only DC and B cells pulsed with the same antigen (Ag) in the micelle form functioned as accessory cells stimulating the primed T cells to proliferate and produce cytokine. In general, iscoms were better inducers of cell proliferation than micelles, Iscoms stimulated more secretion of IL-2 and interferon-gamma (IFN-7) than the micelles, but both antigenic forms stimulated secretion of IL-4. DC and B cells pulsed with iscoms stimulated most efficiently the secretion of IL-2 and IFN-7, DC were superior to the other APC in stimulating primed T cells to secrete IFN-7. On the other hand, micelles stimulated more efficiently than iscoms splenic T cells from micelleprimed as well as iscom-primed mice to secrete IL-10, These data indicate that influenza virus envelope proteins incorporated in iscoms stimulate a broad T cell response, possibly emphasizing a Thl type of response. The same Ag in a micelle form induce a more prominent Th2 type of T cell response. The results indicate that the administration of an Ag in an adjuvant formulation can superimpose a different cytokine profile on the immune response than that induced by the protein Ag alone.

Photosensitizer and Light Pave the Way for Cytosolic Targeting and Generation of Cytosolic CD8 T Cells Using PLGA Vaccine Particles

“…Several approaches have been proposed for the delivery of Ags and drugs to the cytosol, such as cell-penetrating peptides that carry their cargo across the plasma membrane (2, 3), pH-sensitive and fusogenic liposomes that break up phagosomes (4-6), micellebased immune-stimulating complexes that may facilitate Ag cross-presentation (7,8), and recombinantly modified viruses (9)(10)(11) and bacteria (12)(13)(14)(15) that trigger CTLs. Also, microparticles or nanoparticles made from biodegradable polymers, such as poly (lactide-co-glycolide) (PLGA), have been investigated for the cytosolic delivery of vaccines.…”

Cellular Renewal and Improvement of Local Cell Effector Activity in Peritoneal Cavity in Response to Infectious Stimuli

“…As a heterogeneous population, MØ play a wide range of roles in the immune system; they are involved in the removal of apoptotic cells and cellular debris under steady state conditions [3] , microorganism ingestion and elimination [4] , [5] , antigen presentation and consequent T cell activation [6] , [7] , resolution of inflammatory processes, angiogenesis and tissue repair [8] . The functionality of MØ subsets is influenced by factors that include their maturation state and activation profile.…”

Comparison of intranasal with targeted lymph node immunization using PR8‐Flu ISCOM adjuvanted HIV antigens in macaques

“…Moreover, studies in mice have demonstrated potent induction of systemic as well as mucosal immune responses after IN application of ISCOM adjuvant [Hu et al, 2001;Sjolander et al, 2001;Coulter et al, 2003] even against ovalbumin, which is strongly tolerogenic when given alone [Mowat et al, 1993;Hu et al, 2001]. Furthermore, ISCOMs were shown to target dendritic cells (DC) efficiently and to induce an IL-12 mediated cascade of innate immune responses after intraperitoneal injection [Villacres-Eriksson, 1995;Smith et al, 1999]. Studies in mice have also shown strong adjuvant effects of influenza virus or influenza HA subunit in IN immunization protocols [Kang et al, 2004;Yao et al, 2004].…”