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)

Transition from naive to Ag-experienced effector/memory CD4+ T cells is initiated during contact with APC in secondary lymphoid tissue. Here, we demonstrate that the CXCR5 is a marker for recently activated memory CD4+ T cells. CXCR5 is rapidly induced during contact with Ag-presenting dendritic cells, well before T cell expansion and effector cell development, and is irreversibly lost on terminally differentiated effector cells. Furthermore, immunization of human volunteers with a recall Ag results in rapid accumulation of Ag-responsive, CXCR5-expressing CD4+ T cells in peripheral blood. Early acquisition of a new migration program enables T zone CD4+ T cells to develop into follicular B helper T cells or, alternatively, into circulating memory CD4+ T cells. Together, CXCR5 unequivocally defines pre-effector memory CD4+ T cells generated during ongoing immune responses.
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PMID:Cutting edge: induction of follicular homing precedes effector Th cell development. 1171 65

Chemokines and their receptors direct movements and encounters of lymphocytes and professional APC into specific microenvironments of lymphoid tissues. Chemokine receptors such as CCR7, CXCR5 and CCR4 that are differentially expressed and modulated in distinct subsets of T cells contribute to establish functionally and spatially segregated microenvironments within secondary lymphoid tissues where T cell activation and differentiation occur. Here, we have explored the modulation of CCR7, CCR4, CCR8 and CXCR5 expression and chemotactic responsiveness to their ligands during commitment of human naive T cells along the Th1 or Th2 differentiation pathway in vitro. Our results document that activation of human naive T cells and differentiation in Th1 or Th2 cells result in progressive down-modulation of CCR7 expression and CCL19 responsiveness. By contrast, expression of CCR4 and responsiveness to CCL22 is rapidly induced at the early stages of both Th1/Th2 cell development. However, while CCR4 expression is further up-regulated upon differentiation into Th2 cells, it is lost on fully differentiated Th1 cells. CCR8 is detected at later time points than CCR4 and exclusively on differentiated Th2 cells as revealed by analysis of mRNA expression and responsiveness to CCL1. Expression of CXCR5 is transiently induced at the early stages of Th cell differentiation, but with distinct kinetics in developing Th1 and Th2 cells. Analysis of human tonsillar CD4(+) T cells reveals a consistent pattern of chemotactic responsiveness and chemokine receptor expression in distinct transitional stages of human T cell activation and differentiation in vivo.
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PMID:Modulation of chemokine receptor expression and chemotactic responsiveness during differentiation of human naive T cells into Th1 or Th2 cells. 1198 13

Interactions between APC and T lymphocytes have been implicated as a major factor contributing to inflammatory bowel disease. To test whether OX40/OX40L interaction plays a role in chronic intestinal inflammation, we induced chronic colitis using dextran sulfate sodium and treated the mice with a murine fusion protein (OX40-IgG). Treatment resulted in a dose-dependent and significant reduction of intestinal inflammation (46%) as measured by a histologic score. IL-10 and IL-5 production from mesenteric lymph node cells increased 20-fold and 18-fold, respectively. In colonic tissue, IL-10 mRNA levels increased and the expression of T-bet was decreased to 30%. IL-10 neutralization partly inhibited the beneficial effects of OX40-IgG treatment. Surprisingly, despite the reduction of inflammation we found the number and size of colonic lymphoid follicles increased, with an accumulation of CD4(+) cells in the mantle area. In contrast, the number of CD4(+) cells infiltrating the mucosa was significantly reduced, as was their CXCR5 expression (24-fold). We conclude that OX40/OX40L interaction contributes to the perpetuation of chronic colitis partly by suppressing IL-10 production. Furthermore, our data suggest that the OX40/OX40L-induced CXCR5 expression on CD4(+) cells may be important for the inflammatory process by allowing migration to the germinal center for further differentiation of CD4(+) cells before they infiltrate the chronically inflamed mucosa.
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PMID:OX40/OX40L interaction induces the expression of CXCR5 and contributes to chronic colitis induced by dextran sulfate sodium in mice. 1463 34

The immune system has developed several regulatory mechanisms to maintain homeostasis of adaptive immune responses. T-cell programmed death (PD)-1 recognition of B7-H1 (PD-L1) expressed on APC and non-lymphoid tissue regulates T-cell activation. We show that B7-H1(-/-) mice exhibit exacerbated proteoglycan (PG)-induced arthritis and increased Th-1 CD4(+) T-cell responses. Unexpectedly, the PG-specific antibody response in B7-H1(-/-) mice was diminished. A reduction in the number of peanut agglutinin(+) GC coincided with a decrease in CD19(+) GL-7(+) CD95(+) GC B cells that was a result of increased caspase-induced apoptosis. The percent of CD38(+) CD138(+) emerging plasma cells was decreased. B7-H1(-/-) mice exhibited an increased frequency of CD4(+) PD-1(hi) CXCR5(hi) ICOS(hi) CD62L(lo) T follicular helper cells that displayed a hyperactive phenotype with increased expression of mRNA transcripts for Bcl6, IL-21, and the apoptosis-inducer molecule FasL. In cell transfer of B7-H1(-/-) cells into SCID mice, non-B and non-T cells were sufficient to normalize the antibody response, T-cell hyperactivity, and the development of PG-induced arthritis. These findings indicate that B7-H1 on non-B and non-T cells signals through PD-1 on T effector cells to prevent excessive activation and reduce autoimmune arthritis. Furthermore, these findings demonstrate a novel role for B7-H1 expression in promoting B-cell survival by regulating the activation of T follicular helper cell.
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PMID:B7-H1 expression on non-B and non-T cells promotes distinct effects on T- and B-cell responses in autoimmune arthritis. 2106 40

The study was carried out to develop standard indicators of relative and absolute content of main populations of T-helpers in peripheral blood of conditionally healthy donors. The examination was implemented to sampling of 52 healthy individuals (29 males and 23 females) aged 18-65 years (median is 30 years). The multicolor cytofluorimetric analysis was applied using panel of following antibodies: CD45RA-FITC, CD62L-PE, CCR4-PerCP/Cy5.5; CCR6-PE/Cy7, CXCR3-APC, CD3-APC-AF750, CD4-Pacific Blue and CXCR5-Brilliant Violet 510TM. The T-helpers 1 were distributed in populations of cells with phenotypes CXCR5-CXCR3+CCR6-CCR4-, also containing Th9, and CXCR5-CXCR3+CCR6+CCR4- referred as Thl/Thl7. The Th2 were detected an the basis of availability of CCR4 at the absence of all other chemokin receptors. The Thi7, besides Thl/Thi7 mentioned above, were detected in composition of CXCR5-CXCR3-CCR6+CCR4- and CXCR5-CXCR3-CCR6+CCR4+. The last population also contained Th22. The follicular Th which expressed at their surface CXCR5, formed six cellular populations with following phenotypes: CXCR5+CXCR3-CCR6-CCR4- (Tfh/Tfh2), CXCR5+CXCR3-CCR6-CCR4+ (Tfh2), CXCR5+CXCR3-CCR6+CCR4- (Tfh17), CXCR5+CXCR3-CCR6+CCR4+ (Tfh17), CXCR5+CXCR3+CCR6-CCR4- (Tfh1) and CXCR5+CXCR3+CCR6+CCR4- (Tfh1/Tfh17). The relative and absolute content of T-helpers of mentioned phenotypes was established both within the framework of total population CD3+CD4+ of lymphocytes and among "naive" T-helpers (CD45RA-CD62L+), T-helpers of central (CD45RA-CD62L+) and effector (CD45RA- CD62L-) memory and also "terminal-differentiated" CD45RA-positive cells of effector memory with phenotype CD45RA+CD62L-. The study results can be applied as standard indicators under diagnostic of pathologic conditions of immune system.
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PMID:[THE STANDARD VALUES OF SUB-POPULATIONS OF T-HELPERS OF DIFFERENT LEVEL OF DIFFERENTIATION IN PERIPHERAL BLOOD]. 2750 10