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Query: UMLS:C0033036 (APC)
 10,214 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have examined mechanisms of tolerance to circulating self-proteins in mice that are transgenic for human insulin. Normal, nontransgenic mice develop serum antibody responses when injected with human insulin in CFA; syngeneic transgenic mice do not. B cell responsiveness was assessed by immunizing with human insulin coupled to a T-independent Ag, Brucella abortus. No differences were found in the numbers of insulin-specific splenic plaque-forming cells between transgenic and nontransgenic mice suggesting that insulin-specific B cells are not tolerant in transgenic mice. Similarly, APC from transgenic and nontransgenic mice display no differences in their ability to process and present human insulin to human insulin-specific T cells in vitro. However, marked differences were detected between transgenic and nontransgenic T cells. Lymph node T cells from transgenic mice primed with human insulin provided no detectable helper activity for secondary antibody responses to human insulin whereas, lymph node T cells from nontransgenic mice did. Nevertheless, lymph node T cells from transgenic mice developed significant proliferative responses to human insulin. Lymph node T cells obtained from transgenic and nontransgenic mice were fused to BW5147 and human insulin-specific T cell hybridomas were generated. The fact that human insulin-specific T cell hybridomas were obtained from the transgenic mice suggests that these T cells were not clonally deleted. In addition, APC from transgenic mice did not stimulate human insulin-specific hybridomas from normal mice in the absence of exogenous insulin. We suggest that T cells specific for human insulin are not deleted in the thymus of transgenic mice because APC in the thymus do not bear the requisite levels of endogenous human insulin/Ia complexes. Therefore, we conclude that tolerance in the transgenic mice is preserved by peripheral mechanisms.
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PMID:A peripheral mechanism preserves self-tolerance to a secreted protein in transgenic mice. 197 65

Subcutaneous immunization with the thymus independent Ag, TNP-Ficoll, does not elicit plaque-forming cell response from the regional lymph node B cells even though a good response is obtained with the splenic B cells. Lymph node cells respond well to the thymus independent 1 Ag, TNP-Brucella abortus. Because TNP-Ficoll is a soluble Ag and may not be retained well in the lymph nodes, we emulsified it with Freund's adjuvant and injected it into foot pads. This did not result in any antibody response in the popliteal and inguinal lymph nodes though once again splenic B cells gave excellent responses. We find that the in vivo response to TNP-Ficoll can be induced in the lymph node if TNP-Ficoll is injected along with B. abortus in the foot pads of normal mice. This observation could not be repeated in the splenectomized mice implicating the role of the migration of APC or B cells from spleen to lymph nodes. Similar differential responses are obtained from lymph node and splenic B cells in the in vitro cultures. Lymph node cells respond to TNP-Ficoll with the addition of normal irradiated spleen cells but not with Sephadex G-10-passed spleen cells. This shows the absence of APC or lymphokines which stimulate B lymphocytes to respond to TNP-Ficoll in the lymph nodes. We found that IL-1 but not IL-2 or IL-4 was able to induce TNP-Ficoll response from the lymph node B cells.
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PMID:Differential responses of B cells from the spleen and lymph node to TNP-Ficoll. 312 3

IL-12 induction is critical for immune responses against many viruses and intracellular bacterial pathogens. Recent studies suggest that IL-12-secreting dendritic cells (DC) are potent Th1-inducing APC. However, controversy exists concerning the function of DC subsets. Murine studies have suggested that CD8(+) DC preferentially induce Th1 responses, whereas CD8(-) DC induce Th2 development; in this model, different DC subsets prime different responses. Alternatively, the propensity of DC subsets to prime a Th1 response could depend upon the type of initial stimulus. We used a prototypic Th1-inducing adjuvant, heat-killed Brucella abortus (HKBA) to assess stimulation of DC subsets, relationship between Ag burden and IL-12 production, and down-regulation of DC subset IL-12 production by IL-10. In this study, we show that DC were sole producers of IL-12, although most HKBA uptake was by splenic macrophages and granulocytes. More CD8(-) than CD8(+) DC produced IL-12 after HKBA challenge, whereas only CD8(+) DC produced IL-12 after injection of another Th1-promoting microbial substance, soluble Toxoplasma gondii Ags. Studies in IL-10-deficient mice revealed that IL-10 down-regulates frequency and duration of IL-12 production by both DC subsets. In the absence of IL-10, IL-12 expression is enabled in CD11c(low) cells, but not in macrophages or granulocytes. These findings support the concept of DC as the major IL-12 producers in spleens, but challenge the notion that CD8(+) and CD8(-) DC are destined to selectively induce Th1 or Th2 responses, respectively. Thus, the nature of the stimulating substance is important in determining which DC subsets are activated to produce IL-12.
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PMID:IL-12 induction by a TH1-inducing adjuvant in vivo: dendritic cell subsets and regulation by IL-10. 1146 61