Reciprocal expression of CD70 and of its receptor, CD27, in human long term-activated T and natural killer (NK) cells: inverse regulation by cytokines and role in induction of cytotoxicity

Orengo, Anna Maria; Cantoni, Claudia; Neglia, Francesca; Biassoni, Roberto; Ferrini, Silvano

doi:10.1046/j.1365-2249.1997.d01-942.x

Cited by 37 publications

(27 citation statements)

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“…Regulation of CD27 surface expression has been shown to be primarily regulated at transcriptional level [41] and prolonged T cell activation in vitro resulted in increased CD27 expression followed by a decrease on both, protein and mRNA level [42]. Stimulation with PMA resulted in decreased CD27 protein and mRNA expression, showing that CD27 protein level was always reflected by its mRNA level.…”

Section: Discussionmentioning

confidence: 99%

“…TCR/CD3 activation induces CD27 expression, which depends on cytoplasmic cAMP as well as Ca 2+ concentration, whereas protein kinase C (PKC) activation results in decreased CD27 expression [42]. Addition of IL-1, IL-6 or IFN-c has not been shown to influence CD27 expression on T cells [41,43]. A role of IL-4 and TNF-a in regulating CD27 surface expression remains controversial.…”

Section: Discussionmentioning

confidence: 99%

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CD4⁺ T cell help improves CD8⁺ T cell memory by retained CD27 expression

2008

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CD4 + T cell help during the priming of CD8 + T lymphocytes imprints the capacity for optimal secondary expansion upon re-encounter with antigen. Helped memory CD8 + T cells rapidly expand in response to a secondary antigen exposure, even in the absence of T cell help and, are most efficient in protection against a re-infection. In contrast, helpless memory CTL can mediate effector function, but secondary expansion is reduced. How CD4 + T cells instruct CD8 + memory T cells during priming to undergo efficient secondary expansion has not been resolved in detail. Here, we show that memory CTL after infection with lymphocytic choriomeningitis virus are CD27 high whereas memory CTL primed in the absence of CD4 + T cell have a reduced expression of CD27. Helpless memory CTL produced low amounts of IL-2 and did not efficiently expand after restimulation with peptide in vitro. Blocking experiments with monoclonal antibodies and the use of CD27 -/-memory CTL revealed that CD27 ligation during restimulation increased autocrine IL-2 production and secondary expansion. Therefore, regulating CD27 expression on memory CTL is a novel mechanism how CD4 + T cells control CTL memory.Key words: CD27 Á CD4 T cell help Á Costimulation Á LCMV Á T cell memory IntroductionAfter an acute infection, the initial expansion of CTL is determined by a brief period of antigenic stimulation followed by a contraction to a stable pool of long-lived memory cells [1][2][3]. Memory CTL are characterized by an increased frequency of specific CD8 + T cells with a heightened sensitivity to an antigen that has been encountered previously. The cellular basis influencing memory CTL formation has been the focus of extensive research. Several studies highlighted the importance of CD4 + T cells in the generation of CTL memory [4][5][6]. Memory T lymphocytes that are primed in the absence of CD4 + T cell help have a reduced proliferation capacity. In addition, the production of acute effector cytokines and IL-2 are reduced [7]. "Unhelped" CD8 + T cells die upon in vitro re-activation, due to the expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), which is not expressed by "helped" CD8 + memory T cells [8].The mechanisms how CD4 + T cell help drives CD8 + T cell memory has not been resolved in detail. Mice deficient for CD40L have CD8 + memory T cells with reduced function. The CD40-CD40L interaction may be involved in the generation of CTL memory via two mechanisms. First, CD4 + T cells expressing CD40L activate APC through CD40 and these "licensed" APC are then able to drive CD8 + T cell responses [9][10][11]. Secondly, CD4 + T cells expressing CD40L may directly deliver help to CD8 + T cells [7]. Besides the CD40-CD40L interaction, other receptor-ligand interactions such as the CD27-CD70 interaction may be important for generating functional CD8 + memory T cells [12]. In addition, soluble signals may be involved in CD8 + T cell formation. It has been reported that IL-4-secreting CD4 + T cells are involved in the formation of memo...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

CD4⁺ T cell help improves CD8⁺ T cell memory by retained CD27 expression

2008

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“…Interestingly, some glioblastomas also express CD70 (64), and in these tumors, CD70 expression protects the tumor from lysis by CD27-expressing cytotoxic T cells (65). Whereas CD70 serves as the ligand for the CD27 receptor, there is also evidence that CD27 serves as a ligand for the CD70 receptor and induces a signal transduction cascade in CD70 + lymphocytes that results in mitogenic and activating stimulation (45,48,51). Because many CD70…”

Section: Discussionmentioning

confidence: 99%

“…The LD6 and Ki-24 (a gift from Harald Stein, Institut fü r Pathologie, Charité-Campus Benjamin Franklin, Medical University Berlin, Berlin, Germany) antibodies have been described previously (30,51). Control antibodies used were purified murine IgG1 for LD6 experiments and purified murine IgG3 for Ki-23 experiments (both purchased from Sigma, St. Louis, MO).…”

Section: Methodsmentioning

confidence: 99%

Anti-CD70 antibodies: a potential treatment for EBV+ CD70-expressing lymphomas

Israel

Gulley

Elmore

et al. 2005

Molecular Cancer Therapeutics

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“…In normal tissues, CD70 expression is restricted to cells of hematopoietic origin, and it is only transiently induced upon activation of T and B lymphocytes (6,7), natural killer cells (8,9), and maturation of dendritic cells (10,11). As a result, histologic analysis of normal tissues reveals rare CD70-expressing cells only in lymphoid tissues like the thymus, spleen, peripheral lymph nodes, and gut-associated lymphoid tissues (12,13).…”

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confidence: 99%

Preclinical Characterization of SGN-70, a Humanized Antibody Directed against CD70

McEarchern

Smith

McDonagh

et al. 2008

Clinical Cancer Research

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Purpose: CD70 (CD27L) is a member of the tumor necrosis factor family aberrantly expressed on a number of hematologic malignancies and some carcinomas. CD70 expression on malignant cells coupled with its highly restricted expression on normal cells makes CD70 an attractive target for monoclonal antibody (mAb)^based therapies. We developed a humanized anti-CD70 antibody, SGN-70, and herein describe the antitumor activities of this mAb. Experimental Design: CD70 expression on primary tumors was evaluated by immunohistochemical staining of Hodgkin lymphoma, non-Hodgkin lymphoma, multiple myeloma, and renal cell carcinoma tissue microarrays. The CD70-binding and cytotoxic activities of SGN-70 were tested in vitro using a number of cell-based assays. The in vivo antitumor properties of SGN-70 were tested in severe combined immunodeficient mice bearing disseminated lymphoma and multiple myeloma xenografts. Mechanism-of-action studies were conducted using SGN-70v, a variant mAb with equivalent target-binding activity but impaired

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Reciprocal expression of CD70 and of its receptor, CD27, in human long term-activated T and natural killer (NK) cells: inverse regulation by cytokines and role in induction of cytotoxicity

Cited by 37 publications

References 0 publications

CD4⁺ T cell help improves CD8⁺ T cell memory by retained CD27 expression

CD4⁺ T cell help improves CD8⁺ T cell memory by retained CD27 expression

Anti-CD70 antibodies: a potential treatment for EBV+ CD70-expressing lymphomas

Preclinical Characterization of SGN-70, a Humanized Antibody Directed against CD70

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Reciprocal expression of CD70 and of its receptor, CD27, in human long term-activated T and natural killer (NK) cells: inverse regulation by cytokines and role in induction of cytotoxicity

Cited by 37 publications

References 0 publications

CD4+ T cell help improves CD8+ T cell memory by retained CD27 expression

CD4+ T cell help improves CD8+ T cell memory by retained CD27 expression

Anti-CD70 antibodies: a potential treatment for EBV+ CD70-expressing lymphomas

Preclinical Characterization of SGN-70, a Humanized Antibody Directed against CD70

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CD4⁺ T cell help improves CD8⁺ T cell memory by retained CD27 expression

CD4⁺ T cell help improves CD8⁺ T cell memory by retained CD27 expression