Functional analysis of macrophages, B cells and splenic dendritic cells as antigen‐presenting cells in West Nile virus‐specific murine T lymphocyte proliferation

Abstract

Summary I nihis paper, the relative efficacy of macrophages, B cells and splenic dendritic cells (SDC) in presenting West Nile virus (WNV) antigens to WNV memory CD4"'' T cells is examined. The results indicate that, under appropriate conditions, all these ceil types can function as antigen-presenting cells (APC). Li.sicria-mduccii peritoneal macrophages induced higher proliferativc responses than SDC or B cells derived from naive or 14 day WNV-primcd mice. The ability of Z.mma-induced macrophage populations to present antigen was specifically inhibited by anti-Class II major histocompatibility complex (MHC) antibodies. On a cell population basis. B cells obtained from mice primed with WNV 14 days previously evoked higher responses than resting B cells. B eells from mice receiving weekly injections ofWNV over a period of4 weeks elicited optimal responses with lowerdoses of antigen than naive or 14 day WNV-primed B cells. When macrophages were used as APC. addition of specific antibodies to WNV resulted in increased eHicieney of presentation, probably due to increased uptake of antigen by opsonization. In contrast, addition of anti-WNV antibodies to hyperimmune B cells reduced their clficacy presumably by rcdueing uptake of antigen by B eell surface immunoglobulin. When SDC from C57BL/6 mice were used as APC. WN'V-specificproliferative responses were directly related to the number of stimulator cells used, and the background proliferation with moek antigen was two-to five-fold lower than specific responses. Higher levels of background proliferation were stimulated by SDC from CBA/H mice so that the antigen-specific responses were always less than two-fold higher than background.

CD8+T Cells Mediate Recovery andImmunopathology in West Nile VirusEncephalitis

“…The lack of CD4 ϩ and predominance of CD8 ϩ T cells in CNS infiltrates has been observed previously in flavivirus infections (34) and in other viral infections of the CNS, such as lymphocytic choriomeningitis virus infection (8), but no satisfactory explanation has been advanced so far which is able to explain the prevalence of one type of T effector cells over the other. B6 mice are genetically fully competent to respond to WNV antigens, with a vigorous CD4 ϩ T-cell response in the periphery (30). For two reasons, it also seems improbable that the lack of ligand for CD4 ϩ T cells (MHC class II) is responsible for this CD8 ϩ T-cell predominance, as has been proposed by Liu et al (34).…”

Effect of high ligand concentration on West Nile virus‐specific T cell proliferation

“…Preliminary experiments described in detail elsewhere (2) established that priming mice i.v. with 10« p.f.u.…”

“…B cells obtained from three different sources were evaluated for their APC function in the stimulation of WNV-immune CD4+ T cells at four different S : R ratios ranging from 2.0 to 0.25 in two-fold steps. In earlier studies it was observed that WNV-specific T cell proliferative responses were suppressed at a 1/4 dilution of WNV antigen when B+ + + + cells were used as APC (2). Therefore more dilute (1/16) WNV antigen was used to pulse these APC.…”

“…The most extensively studied APC include macrophages, B cells and lymphoid dendritic cells, all of which are capable of endocytosis of foreign antigens, processing of these proteins into small peptides, and presentation of peptide-Class II MHC complexes to T cells. In the course of recent studies (2) evaluating the eflScacy of various APC in presenting antigens of West Nile Virus (WNV) to polyclonal populations of murine, CD4+, WNV-specific T cells it became evident that high APC numbers pulsed with high WNV antigen concentrations suppressed T cell proliferation. These observations were reminiscent of those of Lamb et al Abbreviations used in this paper: APC, antigen-presenting cell(s); B14, B cells derived from 14 day West Nile virus-primed mice; Bo, B cells derived from naive mice; B++++, B cells derived from the mice hyperimmunized with West Nile virus; DC, dendritic cells; DMEM, Dulbecco's modified Eagle's medium; EMEM, Eagle's minimal essential medium; FcR, Receptors for immunoglobulin Fc piece; FCS, fetal calf serum; hkLM, heat-killed Listeria; i.v., intravenous; LM-induced, Listeria-induced; ME, 2-mercaptoethanol; MHC, major histocompatibility complex; NMS, normal mouse serum; PEC, peritoneal exudate cells; p.f.u., plaque forming units; PG, prostaglandins; S : R ratio, stimulator to responder ratio; TcR, T cell receptor; TH-induced, thioglycollate-induced; WNV, West Nile virus.…”

Cytokine-induced killer cells co-cultured with complete tumor antigen-loaded dendritic cells, have enhanced selective cytotoxicity on carboplatin-resistant retinoblastoma cells

“…Our study focused on the two principal players: the T-lymphocytes and the DCs. DCs are the most powerful antigen-presenting cells, with a capacity of antigen-presentation that is hundreds of times more efficient than B lymphocytes and macrophages (29). They can activate resting T-cells and induce the generation of antigen-specific cytotoxic T-lymphocytes, which are the initiators of the immune response (30).…”