In vitro immune responses to a T cell-dependent antigen by cultures of disassociated murine Peyer's patch

Abstract

The first line of defense against pathogens that enter the host by the oral route appears to involve the gut-associated lymphoreticular tissues 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 oflocal 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 (MC)] 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) (5) in GALT, local antibody production does not occur (6, 7). Instead, sensitized lymphocytes leave PP via efferent lymphatics, enter the blood circulation, and selectively populate mucosal sites (8, 9). The lack of local antibody synthesis in PP has been attributed to a deficiency (or architectural separation) of at least one of the three cell types required for immune responses to thymic-dependent (TD) antigens-namely, T and B lymphocytes and macrophages (MF) (see ref. 10 for review).Kagnoff and associates (1,11,12) have reported that dissociated PP cells lack an accessory (Mb) cell population required for in vitro responses to TD antigens. PP from athymic, nude mice lacked both MbD and T cells, and this B cell population was unresponsive to the B-cell mitogen lipopolysaccharide (LPS); responses to the mitogen were restored by exogenously supplied T cells and Mb or 2-mercaptoethanol (11

Cytotoxic Lymphocytes in Mucosal Effector Sites

“…However, the incubation of Peyer's patch lymphocytes with irradiated peritoneal exudate cells and 10% concanavalin A (Con A)-conditioned medium has been shown to result in the generation of cytotoxic activity to Yac-1 target cells (London et al, 1986). These results may be analogous to the observation that Peyer's patches lack terminally differentiated B cells (plasma cells) although they are capable of generating antibody secreting cells in in vitro cultures (Kiyono et al, 1982). In contrast to NK cytotoxicity, normal Peyer's patch lymphocytes lyse the NC-sensitive target WEHI-164 in 16-hr 51 Cr release assays.…”

Decreased Lymphocyte Apoptosis by Anti-Tumor Necrosis Factor Antibody in Peyerʼs Patches After Severe Burn

“…These data suggest that the TNF-rich local microenvironment of the small bowel early after burn may result in a strong proapoptotic signal for both epithelial cells and lymphocytes. Peyer's patches have large numbers of B and ␣␤ T lymphocytes, along with smaller numbers of ␥␦ T lymphocytes (31)(32)(33). As some of these lymphocyte subsets have been found to potentially regulate epithelial cell turnover (10,11), the possibility of immune modulation of mucosal atrophy via a TNF-dependent mechanism after burn is present.…”

Mucosal T Cell Networks: Role of FcαR+T Cells and Ig BFαin Regulation of the IgA Response

“…Treatment of PP with the neutral protease Dispase@ releases all major cell types, including accessory cells and immunocompetent B and T cells [46]. Functional accessory cells include both macrophages [46] and dendritic cells (DC) [52] (Fig.…”

“…PP DC present antigen and clusters of PP DC and T cells, when added to B cell cultures, support polyclonal IgA synthesis [53]. Lymphocytes comprise -80 percent of the total cell population obtained from PP with approximately equal distributions of T and B cells [46]. PP are unique in that a high proportion of B cells bear surface IgA (sTgA') and are thus committed to this isotype.…”