Mucosal Immunoregulation: Environmental Lipopolysaccharide and GALT T Lymphocytes Regulate the IgA Response

Abstract

In this review, we have emphasized: 1) bacterial lipopolysaccharide (LPS) involvement in IgA responses to orally administered thymic-dependent (TD) antigens; 2) characterization of Peyer's patch (PP) lymphoreticular cells; and 3) gastrointestinal immunization with gram negative pathogens and anti-LPS immunity to infection. Gut LPS, which interacts with PP lymphoreticular cells, is a major determinant for host responses to orally administered TD antigens. Bacteroides species are the principal microflora present in the gastrointestinal tract and our studies with phenol-water LPS extracts from Bacteroides fragilis indicate that both polysaccharide and lipid A activate lymphoreticular cells. The B. fragilis lipid A moiety, like that derived from E. coli and Salmonella LPS, induces B cell mitogenic responses in cultures from LPS responsive mice, but does not stimulate C3H/ H3J B cells. The inability of lipid A to stimulate gut-associated lymphoreticular tissue (GALT) cells of C3H/HeJ mice results in the induction of greater T helper cell activity in this tissue in response to orally administered TD antigens and ultimately results in an elevated IgA response pattern. Murine PP contain accessory cells (approximately 1% dendritic cells and 6-8% macrophages) and lymphocytes T (35-38%) and B (40-42%). Recent studies with antigen-specific T cell clones from C3H/ H3J PP have resulted in the isolation of IgA isotype-specific T helper cells (PP Th A cells). PP Th A cells are antigen-specific, bear Fc alpha receptors, and require H-2 histocompatibility with B cells for helper activity. PP Th A cells most effectively collaborate with surface IgA (sIgA)-bearing B cells (IgA committed B cells) for IgA isotype responses. Other studies have shown that PP dendritic cells and T cells form clusters when stimulated in vitro with sodium periodate and that these clusters promote polyclonal IgA responses in B cell cultures. Polyclonal IgA responses in cultures containing PP cell clusters from C3H/ H3J mice are considerably higher than those in identical cultures from LPS responsive mice. In other studies, the environmental influence on GALT B cells and their resultant commitment to IgA isotype is under investigation. CBA/N, X-linked immunodeficient (xid) mice possess an immature splenic B cell population which cannot respond to thymic-independent class-2 (TI-2) or certain TD antigens. However, GALT B cells of xid mice possess a mature Lyb-5+ B cell subpopulation capable of both TI-2 and TD responses.(ABSTRACT TRUNCATED AT 400 WORDS)

CSF-1 (M-CSF) Enhances the Inflammatory Response of Fibronectin-Primed Macrophages: Pathways Involved in Activation of the Cytokine Network

“…The present data indicate that FN served as a stimulant in its own right and induced both resident and elicited PMÊ to release relatively large quantities of IL-6. This elevated cytokine response to FN was not due to endotoxin contamination of reagents or FN since: (1) endotoxin could not be detected in the Limulus assay; (2) similar results were obtained when polymyxin B [17][18][19] was incorporated into the culture medium, and (3) similar results were obtained when PMÊ were isolated from the LPS-hyporesponsive C3H/HeJ strain [15,16]. Resident PMÊ responded significantly more potently to FN than elicited PMÊ, despite the higher proportion of PMÊ in the latter [2,3], and secreted very high levels of IL-6 when CSF-1 was added to the FN.…”

“…The enhanced IL-6 release was not due to contamination of the reagents with endotoxin, as the Limulus assay indicated no contamination of any of the reagents with endotoxin. In addition, resident PMÊ from the LPS-hyporesponsive C3H/HeJ mice [15,16] responded at the same level as B6 PMÊ and the incorporation of polymyxin B into the culture medium [17][18][19] did not influence the responsiveness of the PMÊ (data not shown). The kinetics of IL-6 release by resident PMÊ in response to FN (10 Ìg/ml) and CSF-1 (10 4 U/ml) is shown in figure 2.…”

IgA Nephropathy Is not Induced in Mice by Oral Administration of TNP-Conjugated Ovalbumin

“…These findings refer to the C3D2 and the Balb/c mice, as well as to the LPS resistant C3H/HeJ mice. A higher response could have occurred in the latter strain because it is more sensitive to the induction of an IgA response than LPS responder mice [10,II], Since LPS can function as an adjuvans in a specific immune response, TNP-LPS was administrated for 6 weeks in a last unsuccessful attempt to orally induce an IgA anti-TNP response. There could be several rea sons why our results do not correspond to those of Emancipator et al [5], Conjugation of OVA with TNP will change its net charge, which could interfere with penetration through the mucosa.…”

Mucosal Immunology – With Special Reference to Specific Immune Defence of the Upper Respiratory Tract

“…T cells that mediate B-cell isotype switching directly from IgM to IgA expres sion have been isolated from murine Peyer's patches [23,29]. Observations on human B cells have indicated that this direct pathway may lead preferentially to IgA2 production [22], 'Switch' T cells are unable to induce terminal B-cell differentiation, but 'post switch' T cells favouring IgA production have also been cloned from murine Peyer's patches [35].…”