Lymphocyte activation and effector functions Turning lymphocytes on and off

DeFranco, A L; Weiss, Arthur

doi:10.1016/s0952-7915(98)80160-x

Cited by 7 publications

(5 citation statements)

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“…macrophages and dendritic cells, which present processed antigen bound to major histocompatibility complex molecules, such as human leukocyte antigen (HLA)-DR, on their cell surfaces (DeFranco and Weiss, 1998). Characteristics of lymphocyte activation include expression of cell surface markers of activation, calcium flux, and production of the classic activation lymphokines IL-2 and IFNγ.…”

Section: Introductionmentioning

confidence: 99%

Foreign body-type multinucleated giant cells induced by interleukin-4 express select lymphocyte co-stimulatory molecules and are phenotypically distinct from osteoclasts and dendritic cells

McNally

Anderson

2011

Experimental and Molecular Pathology

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Foreign body-type multinucleated giant cells (FBGC), formed by macrophage fusion, are a prominent cell type on implanted biomaterials, although the roles they play at these and other sites of chronic inflammation are not understood. Why lymphocytes are present in this scenario and the effects of fusing macrophages/FBGC on subsequent lymphocyte responses are also unclear. To address the physiological significance of FBGC in this regard, we employed our in vitro system of interleukin (IL)-4-induced human monocyte-derived macrophage fusion/FBGC formation. Initially, we pursued the identities of lymphocyte co-stimulatory molecules on fusing macrophages/FBGC. In addition, we further compared the FBGC phenotype to that currently associated with osteoclasts and dendritic cells using recognized markers. Immunoblotting of cell lysates and immunochemistry of macrophages/FBGC in situ, revealed that IL-4-induced macrophages/FBGC strongly express HLA-DR, CD98, B7-2 (CD86), and B7-H1 (PD-L1), but not B7-1 (CD80) or B7-H2 (B7RP-1). Furthermore, molecules currently recognized to be expressed on osteoclasts (calcitonin receptor, tartrate-resistant acid phosphatase, RANK) or dendritic cells (CD1a, CD40, CD83, CD95/fas) are undetectable. In contrast, fusing macrophages/FBGC strongly express the macrophage markers αX integrin (CD11c), CD68, and dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN), whereas CD14 is completely down-modulated with IL-4-induced macrophage fusion. These novel data demonstrate that IL-4-induction of macrophage multinucleation/FBGC formation features the acquisition of a CD14-negative phenotypic profile which is distinguishable from that of dendritic cells and osteoclasts, yet potentially exhibits multiple capacities for lymphocyte interactions with resultant lymphocyte down-modulation.

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Section: Introductionmentioning

confidence: 99%

Foreign body-type multinucleated giant cells induced by interleukin-4 express select lymphocyte co-stimulatory molecules and are phenotypically distinct from osteoclasts and dendritic cells

McNally

Anderson

2011

Experimental and Molecular Pathology

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“…For peripheral T cells, the engagement of TCR with foreign antigen presented by self‐MHC leads to cytokine production and cell proliferation. Although much is known about TCR signal transduction pathways involved in peripheral T‐cell activation (Crabtree and Clipstone, 1994; Rao et al ., 1997; DeFranco and Weiss, 1998), little was known about the signaling mechanism involved in thymocyte apoptosis until the discovery of Nur77 as a potential mediator of TCR‐induced thymocyte apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Integration of calcineurin and MEF2 signals by the coactivator p300 during T-cell apoptosis

2000

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T‐cell antigen receptor (TCR)‐induced thymocyte apoptosis is mediated by calcium‐dependent signal transduction pathways leading to the transcriptional activation of members of the Nur77 family. The major calcium‐ and calcineurin‐responsive elements in the Nur77 promoter are binding sites for myocyte enhancer factor‐2 (MEF2). It has been shown that nuclear factor of activated T cells (NFAT) interacts with MEF2D and enhances its transcriptional activity, offering a plausible mechanism of activation of MEF2D by calcineurin. We report here that NFATp synergizes with MEF2D to recruit the coactivator p300 for the transcription of Nur77. Surprisingly, the enhancement of transcriptional activity of MEF2D by NFATp does not require its DNA‐binding activity, suggesting that NFATp acts as a coactivator for MEF2D. Transient co‐expression of p300, MEF2D, NFATp and constitutively active calcineurin is sufficient to recapitulate TCR signaling for the selective induction of the endogenous Nur77 gene. These results implicate NFAT as an important mediator of T‐cell apoptosis and suggest that NFAT is capable of integrating the calcineurin signaling pathway and other pathways through direct protein–protein interaction with other transcription factors.

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“…Lymphocytes have important functions in the immune system 39 . Lymphocyte survival is mainly governed by apoptosis, which is controlled by a complex and multifaceted process 40,41 .…”

Section: Discussionmentioning

confidence: 99%

“…38 Lymphocytes have important functions in the immune system. 39 Lymphocyte survival is mainly governed by apoptosis, which is controlled by a complex and multifaceted process. 40,41 Several surface molecules of lymphocytes including tumour necrotic factor receptor-1 (TNFR1) and Fas play an important role in initiating an intracellular death-signalling pathway that ultimately results in apoptosis.…”

mentioning

confidence: 99%

Apoptosis of circulating lymphocyte in rats with unilateral ureteral obstruction: Role of angiotensin II

Eiam-Ong

Udom

Sueblinvong³

2005

Nephrology

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Lymphocyte activation and effector functions Turning lymphocytes on and off

Cited by 7 publications

References 0 publications

Foreign body-type multinucleated giant cells induced by interleukin-4 express select lymphocyte co-stimulatory molecules and are phenotypically distinct from osteoclasts and dendritic cells

Foreign body-type multinucleated giant cells induced by interleukin-4 express select lymphocyte co-stimulatory molecules and are phenotypically distinct from osteoclasts and dendritic cells

Integration of calcineurin and MEF2 signals by the coactivator p300 during T-cell apoptosis

Apoptosis of circulating lymphocyte in rats with unilateral ureteral obstruction: Role of angiotensin II

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