Biomedical subjects

D M Spalding

Publications and source records attributed to D M Spalding.

21 records · Page 2Linked to original sources

PubMed1984

Mucosal immunoregulation: environmental lipopolysaccharide and GALT T lymphocytes regulate the IgA response.

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)

Animals↗

PubMed1983

Accessory cells in murine Peyer's patch. I. Identification and enrichment of a functional dendritic cell.

Previous studies have suggested that in vitro and in vivo immune responses are defective in Peyer's patch (PP) as a result of a deficiency in accessory cell number or function. However, we report here that enzymatic dissociation of PP does release a cell population with accessory activity in oxidative mitogenesis, i.e., the proliferation of periodate-modified T cells. The accessory activity present in PP is quantitatively similar to that of spleen. Accessory function is mediated by a cell type(s) that has the following characteristics: low buoyant density, lack of adherence to plastic or glass surfaces, lack of Fc receptors, and presence of surface Ia and the 33D1 dendritic cell (DC)-specific determinants. This PP accessory cell was markedly enriched by a novel technique. PP cells formed large aggregates when cultured for 16 h with irradiated, periodate-treated spleen cells. From the clusters we obtained a low density cell population that was 60% Ia positive, 33D1 positive, non-T and non-B, Fc receptor-negative, and dendritic in morphology. The DC-enriched populations were 60-80-fold enriched in accessory function relative to unfractionated PP. We can now compare PP accessory cells with accessory cells from other organs, and try to determine how PP dendritic cells contribute to the unique functions of this lymphoid organ.

Animals↗

PubMed1982

In vivo immune response to a T-cell-dependent antigen by cultures of disassociated murine Peyer's patch.

The first line of defense against pathogens that enter the host by the oral route appears to involve the gut-associated lymphoreticular tissue-e.g., Peyer's patches (PP). Although animals can readily be immunized by orally administered antigen that mobilizes the secretory immune system, there is a total lack of local antibody synthesis in the PP and the cellular basis for this deficiency remains a mystery. A lymphoreticular cell population, obtained when murine PP were treated with a neutral protease (Dispase), consisted of accessory cells [macrophages (MPhi)] and T and B lymphocytes. In vitro cultures of these PP cell preparations with the thymic-dependent antigen sheep erythrocytes (SRBC) resulted in good anti-SRBC plaque-forming cell (PFC) responses. The time courses of these responses were identical to those seen with spleen cell cultures. Submitogenic concentrations of concanavalin A (Con A) and optimal doses of N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) and lipopolysaccharide (LPS) enhanced in vitro responses of PP cell cultures to SRBC. PP possess fully functional antigen-presenting MPhi because incubation of optimal proportions of splenic T and B cells with purified populations of PP MPhi supported good in vitro immune responses. Murine PP possess all of the necessary elements for an IgA immune response because PP cell cultures derived from mice orally primed with SRBC and immunized with SRBC in vitro gave high IgA anti-SRBC PFC responses. All of the adjuvants tested (LPS, MDP, and Con A) enhanced IgA responses in PP cell cultures from orally primed mice; however, Con A induced the greatest enhancement. These results demonstrate that murine PP possess MPhi capable of accessory cell functions for in vitro immune responses and that oral priming with antigen induces the precursor T- and B-cell populations necessary for IgA responses, that are potentiated by adjuvants, in PP cell cultures. Thus, murine PP possess the lymphoreticular cells required for antibody responses; however, the tissue architecture likely prevents local responses in vivo. The finding that enzymatically dissociated PP contain all of the necessary cellular components for antibody synthesis, whereas the in vivo tissue architecture prevents the complex interactions necessary for this response, suggests that the initial inductive events take place in situ, and additional cell interactions are required for final differentiation of IgA-synthesizing plasma cells to occur at distant mucosal sites.

Animals↗