Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033036 (APC)
 10,214 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

MRL/Mp-lpr/lpr (MRL/lpr) mice develop marked lymphadenopathy, characterized predominantly by Thy1+CD3+CD4-CD8- cells ("double negative T cells"; DNT). It is paradoxical that DNT proliferate poorly in vitro when stimulated through CD3 or by mitogens. The hamster mAb H1.2F3, raised against dendritic epidermal DNT, recognizes a very early activation (VEA) Ag, which is generally absent on resting cells but expressed soon after T cell activation with ConA or phorbol ester. Cross-linking of this disulfide-linked dimer in the presence of APC and phorbol ester induces proliferation of normal T cells. Therefore, we tested to see whether MRL/lpr DNT expressed this Ag and whether it might play a role in DNT expansion. Unmanipulated cells from enlarged MRL/lpr lymph nodes expressed VEA in an age-dependent manner, peaking at 3 to 4 mo of age. Only limited expression in a small subset of lymphocytes from the congenic MRL/Mp(-)+/+ strain was seen. VEA expression on freshly harvested MRL/lpr lymphocytes was seen mainly on DNT, yet double staining of the DNT for VEA Ag and three other markers known to be present on lpr DNT showed that the DNT were a heterogeneous population. In addition, some CD4+ T cells expressed VEA Ag. Despite their constitutive VEA Ag expression, MRL/lpr DNT showed no proliferative response to cross-linking with the H1.2F3 antibody. Furthermore, unlike normal T cells, they failed to respond to the antibody even when phorbol ester was added. The addition of supplementary cytokines did not correct this defect. These studies indicate that MRL/lpr DNT constitutively and aberrantly express VEA but do not respond when it is cross-linked. These abnormalities may result from the failure to express Fas, the recently reported apoptosis-inducing receptor defective in lpr mice.
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PMID:Aberrant expression of the very early activation antigen on MRL/Mp-lpr/lpr lymphocytes. 838 Apr 29

Infection of genetically susceptible mice with the LP-BM5 mixture of murine leukemia viruses including an etiologic defective virus (BM5def) causes an immunodeficiency syndrome called murine AIDS (MAIDS). The disease is characterized by interactions between B cells and CD4(+) T cells resulting in polyclonal activation of both cell types. It is known that BM5def is expressed at highest levels in B cells and that B cells serve as viral APC. The CD19-CD21 complex and CD22 on the surface of B cells play critical roles as regulators of B cell responses to a variety of stimuli, influencing cell activation, differentiation, and survival. CD19 integrates positive signals induced by B cell receptor ligation by interacting with the protooncogene Vav, which leads to subsequent tyrosine phosphorylation of this molecule. In contrast, CD22 negatively regulates Vav phosphorylation. To analyze the role of CD19, CD21, Vav, and CD22 in MAIDS, we infected mice deficient in CD19, CD21 (CR2), Vav-1, or CD22 with LP-BM5 murine leukemia viruses. Infected CR2(-/-) mice developed MAIDS with a time course and severity indistinguishable from that of wild-type mice. In contrast, CD19 as well as Vav-1 deficiency restricted viral replication and suppressed the development of typical signs of MAIDS including splenomegaly, lymphadenopathy, and hypergammaglobulinemia. Finally, CD22 deficiency was found to accelerate MAIDS development. These results provide novel insights into the B cell signaling pathways required for normal induction and progression of MAIDS.
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PMID:CD19 signaling pathways play a major role for murine AIDS induction and progression. 1242 39

T lymphocyte responses promote proatherogenic inflammatory events, which are influenced by costimulatory molecules of the B7 family. Effects of negative regulatory members of the B7 family on atherosclerosis have not been described. Programmed death-ligand 1 (PD-L1) and PD-L2 are B7 family members expressed on several cell types, which inhibit T cell activation via binding to programmed death-1 (PD-1) on T cells. In order to test whether the PD-1/PD-L pathway regulates proatherogenic T cell responses, we compared atherosclerotic lesion burden and phenotype in hypercholesterolemic PD-L1/2(-/-)LDLR(-/-) mice and LDLR(-/-) controls. PD-L1/2 deficiency led to significantly increased atherosclerotic burden throughout the aorta and increased numbers of lesional CD4(+) and CD8(+) T cells. Compared with controls, PD-L1/2(-/-)LDLR(-/-) mice had iliac lymphadenopathy and increased numbers of activated CD4(+) T cells. Serum levels of TNF-alpha were higher in PD-L1/2(-/-)LDLR(-/-) mice than in controls. PD-L1/2-deficient APCs were more effective than control APCs in activating CD4(+) T cells in vitro, with or without cholesterol loading. Freshly isolated APCs from hypercholesterolemic PD-L1/2(-/-)LDLR(-/-) mice stimulated greater T cell responses than did APCs from hypercholesterolemic controls. Our findings indicate that the PD-1/PD-L pathway has an important role in downregulating proatherogenic T cell response and atherosclerosis by limiting APC-dependent T cell activation.
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PMID:Proatherogenic immune responses are regulated by the PD-1/PD-L pathway in mice. 1785 43