scholarly journals Recombinant human interferon-inducible protein 10 is a chemoattractant for human monocytes and T lymphocytes and promotes T cell adhesion to endothelial cells.

1993 ◽  
Vol 177 (6) ◽  
pp. 1809-1814 ◽  
Author(s):  
D D Taub ◽  
A R Lloyd ◽  
K Conlon ◽  
J M Wang ◽  
J R Ortaldo ◽  
...  
Keyword(s):  
T Cells ◽  
Endothelial Cells ◽  
Biological Activity ◽  
Cell Adhesion ◽  
Endothelial Cell ◽  
T Cell ◽  
Peripheral Blood ◽  
Human Peripheral Blood ◽  
Inducible Protein ◽  
Interferon Inducible Protein

The human cytokine interferon-inducible protein 10 (IP-10) is a small glycoprotein secreted by activated T cells, monocytes, endothelial cells, and keratinocytes, and is structurally related to a family of chemotactic cytokines called chemokines. Although this protein is present in sites of delayed-type hypersensitivity reactions and lepromatous leprosy lesions, the biological activity of IP-10 remains unknown. We report here that recombinant human IP-10 stimulated significant in vitro chemotaxis of human peripheral blood monocytes but not neutrophils. Recombinant human IP-10 also stimulated chemotaxis of stimulated, but not unstimulated, human peripheral blood T lymphocytes. Phenotypic analysis of the stimulated T cell population responsive to IP-10 demonstrated that stimulated CD4+ and CD29+ T cells migrated in response to IP-10. This resembles the biological activity of the previously described T cell chemoattractant RANTES. Using an endothelial cell adhesion assay, we demonstrated that stimulated T cells pretreated with optimal doses of IP-10 exhibited a greatly enhanced ability to bind to an interleukin 1-treated endothelial cell monolayer. These results demonstrate that the IP-10 gene encodes for an inflammatory mediator that specifically stimulates the directional migration of T cells and monocytes as well as potentiates T cell adhesion to endothelium.

scholarly journals The induction of 72-kD gelatinase in T cells upon adhesion to endothelial cells is VCAM-1 dependent.

1994 ◽  
Vol 125 (5) ◽  
pp. 1165-1178 ◽  
Author(s):  
A M Romanic ◽  
J A Madri
Keyword(s):  
T Cells ◽  
Endothelial Cells ◽  
Cell Adhesion ◽  
Endothelial Cell ◽  
T Cell ◽  
Cell Surface ◽  
Cell Monolayer ◽  
Brain Parenchyma ◽  
Protein Activity ◽  
Gelatinase Activity

T cell extravasation from the bloodstream into the perivascular tissue during inflammation involves transmigration through the endothelial cell layer and basement membrane into the interstitial matrix. The specific mechanisms by which T cells transmigrate, however, are poorly understood. Matrix degradation by enzymes such as 72-kD gelatinase has been implicated as an important component in tissue invasion by various types of cells. In this study, we have demonstrated that 72-kD gelatinase is induced in T cells upon adhesion to endothelial cells. We also provide evidence that the induction of 72-kD gelatinase is mediated by binding to vascular cell adhesion molecule-1 (VCAM-1). The T cells used in this study were cloned murine Th1 cells antigenic to myelin basic protein. These cells express very late antigen-4 on their cell surface and have been shown to infiltrate the brain parenchyma and cause experimental autoimmune encephalomyelitis when infused into normal mice (Baron, J. L., J. A. Madri, N. H. Ruddle, G. Hashim, and C. A. Janeway. 1993. J. Exp. Med. 177:57-68). In the experiments presented here, T cells were cocultured with VCAM-1-positive and -negative endothelial cells grown in a monolayer in order to study the expression of 72-kD gelatinase upon T cell adhesion. Additional experiments were conducted in which T cells were cocultured with VCAM-1 positive cells grown on microporous membranes suspended in transwells to study 72-kD gelatinase following T cell transmigration. T cells were also incubated with recombinant VCAM-1 in order to study the role of VCAM-1 in inducing 72-kD gelatinase. The results demonstrated that T cells adhered to both VCAM-1-positive and -negative endothelial cells. T cells that adhered to the VCAM-1-positive endothelial cells exhibited an induction in 72-kD gelatinase protein, activity, and mRNA whereas 72-kD gelatinase was not induced in the T cells that adhered to the VCAM-1-negative endothelial cells. Incubating T cells with recombinant VCAM-1 coated onto tissue culture plastic showed that T cells adhered to the molecule and that adhesion to recombinant VCAM-1 was sufficient to induce 72-kD gelatinase. Further, T cells that had transmigrated through a VCAM-1-positive endothelial cell monolayer exhibited 72-kD gelatinase activity but not mRNA expression. In addition, 72-kD gelatinase was detected on the cell surface of the transmigrated T cells by FACS analysis. In other experiments, TIMP-2 was added to the transmigration studies and was shown to reduce T cell transmigration.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals CD31 expressed on distinctive T cell subsets is a preferential amplifier of beta 1 integrin-mediated adhesion.

1992 ◽  
Vol 176 (1) ◽  
pp. 245-253 ◽  
Author(s):  
Y Tanaka ◽  
S M Albelda ◽  
K J Horgan ◽  
G A van Seventer ◽  
Y Shimizu ◽  
...  
Keyword(s):  
T Cells ◽  
Endothelial Cells ◽  
Cell Adhesion ◽  
Endothelial Cell ◽  
T Cell ◽  
Cd8 T Cells ◽  
Cell Adhesion Molecule ◽  
T Cell Subsets ◽  
Beta 2 ◽  
Endothelial Cell Adhesion

The CD31 (platelet endothelial cell adhesion molecule-1 [PECAM-1]/endothelial cell adhesion molecule [endoCAM]) molecule expressed on leukocytes, platelets, and endothelial cells is postulated to mediate adhesion to endothelial cells and thereby function in immunity, inflammation, and wound healing. We report the following novel features of CD31 which suggests a role for it in adhesion amplification of unique T cell subsets: (a) engagement of CD31 induces the adhesive function of beta 1 and beta 2 integrins; (b) adhesion induction by CD31 immunoglobulin G (IgG) monoclonal antibodies (mAbs) is sensitive, requiring only bivalent mAb; (c) CD31 mAb induces adhesion rapidly, but it is transient; (d) unique subsets of CD4+ and CD8+ T cells express CD31, including all naive (CD45RA+) CD8 T cells; and (e) CD31 induction is selective, inducing adhesive function of beta 1 integrins, particularly very late antigen-4, more efficiently than the beta 2 integrin lymphocyte function-associated antigen-1. Conversely, CD3 is more effective in inducing beta 2-mediated adhesion. Taken together, these findings indicate that unique T cell subsets express CD31, and CD31 has the capacity to induce integrin-mediated adhesion of T cells in a sensitive and selective fashion. We propose that, in collaboration with other receptors/ligands, CD31 functions in an "adhesion cascade" by amplifying integrin-mediated adhesion of CD31+ T cells to other cells, particularly endothelial cells.

Endothelial cell lymphocyte function-associated antigen-3 and an unidentified ligand act in concert to provide costimulation to human peripheral blood CD4+ T cells

1991 ◽  
Vol 137 (1) ◽  
pp. 150-163 ◽  
Author(s):  
Caroline O.S. Savage ◽  
Christopher C.W. Hughes ◽  
R.Blake Pepinsky ◽  
Barbara P. Wallner ◽  
Arnold S. Freedman ◽  
...  
Keyword(s):  
T Cells ◽  
Endothelial Cell ◽  
Peripheral Blood ◽  
Cd4 T Cells ◽  
Human Peripheral Blood ◽  
Lymphocyte Function

Effect of CD28 signal transduction on c-Rel in human peripheral blood T cells

1994 ◽  
Vol 14 (12) ◽  
pp. 7933-7942
Author(s):  
R G Bryan ◽  
Y Li ◽  
J H Lai ◽  
M Van ◽  
N R Rice ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Peripheral Blood ◽  
Cell Activation ◽  
Nuclear Translocation ◽  
Human Peripheral Blood ◽  
Interleukin 2 ◽  
Cell Receptor ◽  
Cd28 Costimulation

Optimal T-cell activation requires both an antigen-specific signal delivered through the T-cell receptor and a costimulatory signal which can be delivered through the CD28 molecule. CD28 costimulation induces the expression of multiple lymphokines, including interleukin 2 (IL-2). Because the c-Rel transcription factor bound to and activated the CD28 response element within the IL-2 promoter, we focused our study on the mechanism of CD28-mediated regulation of c-Rel in human peripheral blood T cells. We showed that CD28 costimulation accelerated the kinetics of nuclear translocation of c-Rel (and its phosphorylated form), p50 (NFKB1), and p65 (RelA). The enhanced nuclear translocation of c-Rel correlated with the stimulation of Il-2 production and T-cell proliferation by several distinct anti-CD28 monoclonal antibodies. This is explained at least in part by the long-term downregulation of I kappa B alpha following CD28 signalling as opposed to phorbol myristate acetate alone. Furthermore, we showed that the c-Rel-containing CD28-responsive complex is enhanced by, but not specific to, CD28 costimulation. Our results indicate that c-Rel is one of the transcription factors targeted by CD28 signalling.

scholarly journals Human interferon-inducible protein-10 induces mononuclear cell infiltration in mice and promotes the migration of human T lymphocytes into the peripheral tissues and human peripheral blood lymphocytes-SCID mice

Blood ◽  
1996 ◽  
Vol 87 (4) ◽  
pp. 1423-1431 ◽  
Author(s):  
DD Taub ◽  
DL Longo ◽  
WJ Murphy
Keyword(s):  
T Cell ◽  
Mononuclear Cell ◽  
Human Peripheral Blood ◽  
Peripheral Blood Lymphocytes ◽  
Cell Infiltration ◽  
Mononuclear Cell Infiltration ◽  
Human T Cell ◽  
Inducible Protein ◽  
Interferon Inducible Protein

The human cytokine, interferon-inducible protein-10 (IP-10), is a small glycoprotein secreted by activated monocytes, T cells, keratinocytes, astrocytes, and endothelial cells and is structurally related to the alpha subfamily of chemotactic cytokines called chemokines (Taub and Oppenheim, Cytokine 5:175, 1993). However, in contrast to other alpha chemokines that induce neutrophil migration, IP-10 has been shown to chemoattract monocytes and T lymphocytes in vitro, suggesting a role in T-cell-mediated immune responses. We therefore examined the effects of human IP-10 after in vivo administration. IP-10 induces significant mononuclear cell infiltration after subcutaneous injections in normal mice. In an effort to study the in vivo effects of IP-10 on human leukocyte migration, we then examined the ability of recombinant human IP-10 (rhIP-10) to induce human-T-cell infiltration using a human/severe combined immune deficiency (SCID) mouse model. SCID mice received an intraperitoneal injection of human peripheral blood lymphocytes (10(8) cells), followed by a subcutaneous injection of rhIP- 10 (1 micrograms/injection) in the hind flank for 4 hours or sequential injections for 3 days. The skin and underlying tissue from the rhIP-10 injection site were then biopsied and examined for the extent of mononuclear cell infiltration. rhIP-10 again induced significant mononuclear cell accumulation 72 hours after injection. Immunohistologic evaluation determined that a significant number of human CD3+ T cells were recruited in response to rhIP-10 injections. These results show that rhIP-10 is capable of inducing human T-cell migration in vivo and may play an important role in monocyte and lymphocyte recruitment into inflammatory sites.

Age-related increase of frequency of a new, phenotypically distinct subpopulation of human peripheral blood T cells expressing lowered levels of CD4

Blood ◽  
2001 ◽  
Vol 98 (4) ◽  
pp. 1100-1107 ◽  
Author(s):  
Ewa Bryl ◽  
Magdalena Gazda ◽  
Jerzy Foerster ◽  
Jacek M. Witkowski
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Peripheral Blood ◽  
Human Peripheral Blood ◽  
The Elderly ◽  
Cell Subpopulation ◽  
Cell Phenotype ◽  
Receptor Complexes ◽  
Age Related

Aging is associated with modifications of T-cell phenotype and function, leading to impaired activation in response to both new and recall antigens. It is not known if T-cell activation results in elimination of a number of the CD4 molecules from the cell surface, as is the case with CD3/T-cell receptor complexes, or how aging influences the process. The T cells of young and elderly donors with reduced expression of CD4 were examined to see whether these cells exhibit other phenotypic features suggesting their active state. It was found that T lymphocytes expressing CD4 can be divided into 2 semidiscrete subpopulations: the major (CD4+) population, in which the level of expression of CD4 is constant and high, and a minor population (CD4lo), in which the expression of CD4 can be up to an order of magnitude lower than on the CD4+ cells. The proportion of CD4locells is age dependent and highly variable in the apparently healthy human population, with the expression of CD4 ranging from around 10% of all peripheral blood lymphocytes in the young to more than 30% in the elderly. Lowered expression of CD4 is correlated with a reduced expression of CD3, as well as with a decreased amount of CD28 and CD95Fas. Activation of CD4lo cells is suggested by their expression of CD25 and increased amounts of HLA-DR. Phenotypic characteristics of the CD4lo T-cell subpopulation suggest that it might be formed by (perhaps chronically) activated, temporarily apoptosis-resistant cells, possibly accumulating in the elderly.

scholarly journals Direct demonstration of the clonogenic potential of every human peripheral blood T cell. Clonal analysis of HLA-DR expression and cytolytic activity.

1983 ◽  
Vol 157 (2) ◽  
pp. 743-754 ◽  
Author(s):  
A Moretta ◽  
G Pantaleo ◽  
L Moretta ◽  
J C Cerottini ◽  
M C Mingari
Keyword(s):  
T Cells ◽  
T Cell ◽  
Peripheral Blood ◽  
Human Peripheral Blood ◽  
Cell Populations ◽  
Target Cells ◽  
Flow Cytofluorometry ◽  
Hla Dr ◽  
Clonogenic Potential ◽  
Precursor Frequency

In an attempt to determine the clonogenic properties of human peripheral blood T cells, we have developed a limiting dilution microculture system using phytohemagglutinin (PHA) as T cell activator and supernatant from PHA-stimulated spleen cultures as a source of T cell growth factors. The frequencies of cells capable of extensive proliferation under these culture conditions were 0.52-0.73, 0.98-1.11, and less than 0.02 in peripheral blood mononuclear, E-rosette-positive, and E-rosette-negative cell populations, respectively. The clonogenic potential of virtually all T cells was confirmed in experiments using single cells isolated by micromanipulation. Clone size ranged between 5 and 30 X 10(4) cells on day 14 of culture. The same microculture system was used to determine the precursor frequency of all cytolytic T lymphocytes (CTL-P). As assessed by a lectin-dependent 51Cr release assay, the CTL-P frequency in purified T cell populations ranged between 0.30 and 0.34. In comparison, the precursor frequency of T cells capable of lysing K562 target cells was ranging between 0.14 and 0.16. Parallel analysis of individual clonal cultures for both lytic activities showed that 50% of the clones exhibiting lectin-dependent lysis were also active against K562 target cells. All of the proliferating clones expressed HLA-DR antigens, although to a varying degree as assessed by flow cytofluorometry. Given the high cloning efficiency of this culture system, it appears now possible to determine the precursor frequencies of the various classes of functional cells in T cell populations.

DAP10 Costimulates Chimeric Receptor-Mediated T Cell Responses to Tumor Antigen.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3052-3052
Author(s):  
Bianca Altvater ◽  
Sibylle Pscherer ◽  
Heribert Juergens ◽  
Claudia Rossig
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Cells ◽  
T Cell Activation ◽  
Adoptive Immunotherapy ◽  
Peripheral Blood ◽  
Cell Activation ◽  
Human Peripheral Blood ◽  
Cytokine Secretion ◽  
Immunotherapy Of Cancer

Abstract Chimeric receptors (chRecs) combining extracellular recognition domains with the T cell receptor ζ an redirect the cellular immune response of primary T-cells to tumor cells. T cell activation by chRec induces efficient cytokine release and cytotoxicity, however, it fails to mediate proliferative responses, limiting the usefulness of chRec-gene-modified T cells for adoptive immunotherapy of cancer. Inclusion of a CD28 costimulatory signaling component in the chRec endodomain enhances antigen-specific proliferation. Whereas the signal mediated by ligation of CD28 is of crucial importance for the activation of resting CD4+ T cells, further molecules with costimulatory functions have contributory roles. NKG2D is a stimulatory receptor that was first identified in NK cells, but is also expressed in cytotoxic T cells and positively modulates CD8+ T cell immune responses. We hypothesized that inclusion of the NKG2D-associated signaling domain DAP10 would enhance the capacity of chRecs to induce tumor-specific activation and proliferation of in vitro expanded effector T cells. Based on a GD2-specific scFv, we generated chRecs containing either the DAP10 signaling chain alone (14.G2a-DAP10) or combined with TCRζ 14.G2a-DAP10ζ), and expressed them in nonspecifically activated human peripheral blood T cells of three individual donors by retroviral gene transfer. As controls, T cells were transduced with 14.G2a-ζ and -CD28ζ chRec. High chRec surface expression was obtained with all four constructs (55±11%, ζ; 85±3, CD28ζ; 68±5%, DAP10; 78±1%; DAP10ζ). Immunophenotypes were dominated by a CD3+CD8+ population in all cell cultures. Whereas DAP10 alone failed to mediate specific tumor cell lysis, 51Cr release assays revealed efficient and comparable lysis of GD2+ tumor targets by T cells transduced with all ζ-containing constructs, with 49±8% (ζ), 52±7% (CD28ζ), and 52±18% (DAP10ζ) cytolysis at an effector-to-target ratio of 40:1. Intracellular cytokine secretion by chRec+ T cells was induced in response to tumor targets by 14.G2a-ζ (up to 37% IFN-γ secreting cells), CD28ζ, and DAPζ (both up to 22%), but not by DAP10 alone (0,2%). Weekly stimulation with tumor cells for 6 weeks induced only limited expansion of T cells transduced with 14.G2a-ζ (7–45fold) or with 14.G2a-DAP10 (14–26-fold). Adding CD28 or DAP10 domains significantly enhanced expansion by a comparable degree (270–483-fold and 126–436-fold, respectively). Thus, while neither CD28 nor DAP10 enhances antigen-specific cytokine secretion and cytolysis, DAP10 signaling can completely replace CD28 signaling in costimulating antigen-specific proliferation of peripheral blood T cells. DAP10-containing chRec may be a powerful new tool for adoptive immunotherapy of cancer.

scholarly journals Interleukin 15 Induces Endothelial Hyaluronan Expression in Vitro and Promotes Activated T Cell Extravasation through a Cd44-Dependent Pathway in Vivo

1999 ◽  
Vol 190 (1) ◽  
pp. 9-20 ◽  
Author(s):  
Pila Estess ◽  
Animesh Nandi ◽  
Mansour Mohamadzadeh ◽  
Mark H. Siegelman
Keyword(s):  
T Cells ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
T Cell ◽  
Microvascular Endothelial Cell ◽  
Dependent Manner ◽  
Cell Recruitment ◽  
Microvascular Endothelial ◽  
Dependent Pathway

T cell recruitment to extralymphoid tissues is fundamental to the initiation and perpetuation of the inflammatory state during immune and autoimmune responses. Interleukin (IL)-15 is a proinflammatory cytokine whose described functions largely overlap with those of IL-2. The latter is attributable in large part to its binding of the heterotrimeric receptor that contains the β and γ chains of the IL-2R in combination with an unique IL-15Rα chain. However, unlike IL-2, IL-15 and its receptor have a wide tissue and cell type distribution, including endothelial cells. Here, we examine the effect of IL-15 on hyaluronan expression by endothelial cells, and investigate its role in vivo in promoting the extravasation of antigen-activated T cells through a CD44-dependent pathway. The expression of hyaluronan on primary endothelial cells and microvascular endothelial cell lines is induced by IL-15, whereas IL-2 has no such activity. Moreover, intraperitoneal administration of IL-15 or TNF-α in the absence of other exogenous proinflammatory stimuli allows the extravasation of superantigen-stimulated T cells into this site in vivo in a CD44-dependent manner. T cell recruitment induced by IL-15 requires expression of an intact IL-2Rβ chain, indicating that IL-15 operates in this context through the traditional IL-15R. The results suggest that IL-15 can regulate endothelial cell function and thereby enables a CD44-initiated adhesion pathway that facilitates entry of activated T lymphocytes into inflammatory sites. They further demonstrate a novel role for IL-15 (distinct from any of IL-2) in regulating microvascular endothelial cell adhesive function, help to understand the role of IL-15R expression on endothelium, and further support a central position for this cytokine in orchestrating multiple sequential aspects of T cell effector function and therefore chronic inflammatory processes.

scholarly journals Thiols decrease human interleukin (IL) 4 production and IL-4-induced immunoglobulin synthesis.

1995 ◽  
Vol 182 (6) ◽  
pp. 1785-1792 ◽  
Author(s):  
P Jeannin ◽  
Y Delneste ◽  
S Lecoanet-Henchoz ◽  
J F Gauchat ◽  
P Life ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
Peripheral Blood ◽  
Messenger Rna ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Dependent Manner ◽  
Dose Dependent

N-Acetyl-L-cysteine (NAC) is an antioxidant precursor of intracellular glutathione (GSH), usually given in human as a mucolytic agent. In vitro, NAC and GSH have been shown to act on T cells by increasing interleukin (IL) 2 production, synthesis and turnover of IL-2 receptors, proliferation, cytotoxic properties, and resistance to apoptosis. We report here that NAC and GSH decrease in a dose-dependent manner human IL-4 production by stimulated peripheral blood T cells and by T helper (Th) 0- and Th2-like T cell clones. This effect was associated with a decrease in IL-4 messenger RNA transcription. In contrast, NAC and GSH had no effect on interferon gamma and increased IL-2 production and T cell proliferation. A functional consequence was the capacity of NAC and GSH to selectively decrease in a dose-dependent manner IL-4-induced immunoglobulin (Ig) E and IgG4 production by human peripheral blood mononuclear cells. Interestingly, NAC and GSH also acted directly on purified tonsillar B cells by decreasing the mature epsilon messenger RNA, hence decreasing IgE production. In contrast, IgA and IgM production were not affected. At the same time, B cell proliferation was increased in a dose-dependent manner. Not all antioxidants tested but only SH-bearing molecules mimicked these properties. Finally, when given orally to mice, NAC decreased both IgE and IgG1 antibody responses to ovalbumin. These results demonstrate that NAC, GSH, and other thiols may control the production of both the Th2-derived cytokine IL-4 and IL-4-induced Ig in vitro and in vivo.

Sign in / Sign up

Export Citation Format

Share Document