scholarly journals Interleukin 2 induction of pore-forming protein gene expression in human peripheral blood CD8+ T cells.

1990 ◽  
Vol 171 (4) ◽  
pp. 1269-1281 ◽  
Author(s):  
M J Smyth ◽  
J R Ortaldo ◽  
Y Shinkai ◽  
H Yagita ◽  
M Nakata ◽  
...  
Keyword(s):  
T Cells ◽  
Mrna Expression ◽  
Cd8 T Cells ◽  
Peripheral Blood ◽  
Human Peripheral Blood ◽  
Interleukin 2 ◽  
Cytotoxic Lymphocytes ◽  
Mrna Levels ◽  
Cytotoxic Potential

Our studies have analyzed pore-forming protein (PFP) mRNA expression in resting and stimulated human peripheral blood CD3- large granular lymphocytes (LGL), CD3+ T cells, and their CD4+ or CD8+ subsets. Signals that stimulate T cells to develop cytotoxic activity (i.e., IL-2 or OKT-3 mAb) led to the induction of PFP mRNA in T cells. The data indicated that IL-2 directly increased PFP mRNA in the CD8+ subset of T cells, in the absence of new DNA or protein synthesis. Abrogation of IL-2-induced PFP mRNA expression and cytotoxic potential of T cells by the anti-p75 IL-2 receptor mAb suggested that low numbers of p75 IL-2 receptors on CD8+ T cells were capable of transducing signals responsible for these IL-2-induced effects. The induction of T cell PFP mRNA via CD3, using OKT-3 mAb, was less rapid but greater than that caused by IL-2; however, a combination of PMA and ionomycin, which bypasses crosslinking of the TCR/CD3 complex, could not mimic this increase in PFP mRNA levels in T cells. The role of second messenger systems in regulating PFP mRNA expression remains to be determined. In contrast, high constitutive PFP mRNA expression was observed in CD3- LGL and these mRNA levels could not be enhanced by stimulation with IL-2. The cytotoxic potential of peripheral blood T cells and LGL induced in response to IL-2 correlated with IL-2-induced PFP mRNA levels in these cells and was consistent with PFP being one of several important molecules involved in the effector function of cytotoxic lymphocytes.

scholarly journals Activation of peripheral blood T cells via the p75 interleukin 2 receptor.

1989 ◽  
Vol 170 (4) ◽  
pp. 1445-1450 ◽  
Author(s):  
H Yagita ◽  
M Nakata ◽  
A Azuma ◽  
T Nitta ◽  
T Takeshita ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
T Cells ◽  
Nk Cells ◽  
Cd8 T Cells ◽  
Peripheral Blood ◽  
Human Peripheral Blood ◽  
Interleukin 2 ◽  
Constitutive Expression ◽  
Cytolytic Activity ◽  
Maximal Inhibition

By using mAb and flow cytometry, a constitutive expression of the p75 IL-2R was revealed in human peripheral blood CD8+ T cells and TCR delta-1+ T cells as well as in CD16+ NK cells. Anti-p75 IL-2R mAb almost completely inhibited the induction of cytolytic activity in these T cells by brief exposure to IL-2, as estimated by anti-TCR/CD3 mAb-targeted cytotoxicity. While anti-p55 IL-2R mAb alone inhibited the response only modestly, maximal inhibition was achieved by combining both anti-p55 and anti-p75 IL-2R mAbs. These results indicate that the p75 IL-2R constitutively expressed on peripheral blood CD8+ T cells and TCR delta-1+ T cells is predominantly responsible for the direct activation of these cells by IL-2.

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 Polyclonal activation of human B lymphocytes by Fc fragments. I. Characterization of the cellular requirements for Fc fragment-mediated polyclonal antibody secretion by human peripheral blood B lymphocytes.

1981 ◽  
Vol 154 (3) ◽  
pp. 778-790 ◽  
Author(s):  
E L Morgan ◽  
W O Weigle
Keyword(s):  
T Cells ◽  
B Lymphocytes ◽  
Polyclonal Antibody ◽  
Peripheral Blood ◽  
Human Peripheral Blood ◽  
Cell Lineage ◽  
Fc Fragment ◽  
Antibody Secretion

Fc fragments derived from human immunoglobulin were found to be capable of inducing both a proliferative and polyclonal antibody response in human peripheral blood lymphocyte cultures. The cell population proliferating in response to Fc fragments belongs to the B cell lineage. Expression of polyclonal antibody formation requires the presence of both adherent monocytes and T cells. The role of the monocyte is to enzymatically cleave the Fc fragment into 19,000 mol wt Fc subfragments that are then able to induce polyclonal antibody secretion. Stimulation of polyclonal antibody production by Fc subfragments occurs in the absence of adherent monocytes but still requires the presence of T cells.

scholarly journals Identification of Cytolytic CD161−CD56+ Regulatory CD8 T Cells in Human Peripheral Blood

PLoS ONE ◽  
2013 ◽  
Vol 8 (3) ◽  
pp. e59545 ◽  
Author(s):  
Dan Hu ◽  
Howard L. Weiner ◽  
Jerome Ritz
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Peripheral Blood ◽  
Human Peripheral Blood

scholarly journals Immune Mediators in Osteoarthritis: Infrapatellar Fat Pad-Infiltrating CD8+ T Cells Are Increased in Osteoarthritic Patients with Higher Clinical Radiographic Grading

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Jirun Apinun ◽  
Panjana Sengprasert ◽  
Pongsak Yuktanandana ◽  
Srihatach Ngarmukos ◽  
Aree Tanavalee ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Peripheral Blood ◽  
Underlying Mechanism ◽  
Infrapatellar Fat Pad ◽  
Fat Pad ◽  
Immune Mediators ◽  
Adaptive Immune Cells ◽  
Radiographic Grading

Osteoarthritis is a condition of joint failure characterized by many pathologic changes of joint-surrounding tissues. Many evidences suggest the role of both innate and adaptive immunity that interplay, resulting either in initiation or in progression of osteoarthritis. Adaptive immune cells, in particular T cells, have been demonstrated to play a role in the development of OA in animal models. However, the underlying mechanism is yet unclear. Our aim was to correlate the frequency and phenotype of tissue-infiltrating T cells in the synovial tissue and infrapatellar fat pad with radiographic grading. Our results show that CD8+ T cells are increased in osteoarthritic patients with higher radiographic grading. When peripheral blood CD8+ T cells were examined, we show that CD8+ T cells possess a significantly higher level of activation than its CD4+ T cell counterpart (P<0.0001). Our results suggest a role for CD8+ T cells and recruitment of these activated circulating peripheral blood CD8+ T cells to the knee triggering local inflammation within the knee joint.

scholarly journals Response of resting human peripheral blood natural killer cells to interleukin 2.

1984 ◽  
Vol 160 (4) ◽  
pp. 1147-1169 ◽  
Author(s):  
G Trinchieri ◽  
M Matsumoto-Kobayashi ◽  
S C Clark ◽  
J Seehra ◽  
L London ◽  
...  
Keyword(s):  
T Cells ◽  
Nk Cells ◽  
Natural Killer ◽  
Peripheral Blood ◽  
Nk Cell ◽  
Human Peripheral Blood ◽  
Interleukin 2 ◽  
Cell Activity ◽  
Experimental Conditions ◽  
Ifn Gamma

The present study shows that recombinant interleukin 2 (IL-2) purified to homogeneity induces a rapid and potent enhancement of spontaneous cytotoxicity of human peripheral blood lymphocytes. The cells mediating cytotoxicity after 18-h treatment with IL-2 have surface markers of natural killer (NK) cells and are generated from the peripheral blood subset containing spontaneous cytotoxic cells. A parallel production of gamma interferon (IFN-gamma) is induced by recombinant IL-2 (rIL-2), and NK cells appear to be the major producer cells, whereas T cells are unable to produce IFN-gamma under these experimental conditions. However, the kinetics of the enhancement of cytotoxicity are faster than those of IFN-gamma production, and monoclonal anti-IFN-gamma antibodies do not suppress this effect, making it unlikely that the IFN-gamma produced is responsible for the enhancement. The enhancement of NK cell activity induced by rIL-2 precedes any proliferative response of the lymphocytes, which is instead observed in longer-term cultures of both NK and T cells.

scholarly journals Human plasmacytoid dendritic cells efficiently cross-present exogenous Ags to CD8+ T cells despite lower Ag uptake than myeloid dendritic cell subsets

Blood ◽  
2013 ◽  
Vol 121 (3) ◽  
pp. 459-467 ◽  
Author(s):  
Jurjen Tel ◽  
Gerty Schreibelt ◽  
Simone P. Sittig ◽  
Till S. M. Mathan ◽  
Sonja I. Buschow ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Cd8 T Cells ◽  
Peripheral Blood ◽  
Human Peripheral Blood ◽  
Adaptive Immune System ◽  
Plasmacytoid Dendritic Cells ◽  
Cell Responses ◽  
Adaptive Immune ◽  
Antitumor Immunotherapy

Abstract In human peripheral blood, 4 populations of dendritic cells (DCs) can be distinguished, plasmacytoid dendritic cells (pDCs) and CD16+, CD1c+, and BDCA-3+ myeloid DCs (mDCs), each with distinct functional characteristics. DCs have the unique capacity to cross-present exogenously encountered antigens (Ags) to CD8+ T cells. Here we studied the ability of all 4 blood DC subsets to take up, process, and present tumor Ags to T cells. Although pDCs take up less Ags than CD1c+ and BDCA3+ mDCs, pDCs induce potent Ag-specific CD4+ and CD8+ T-cell responses. We show that pDCs can preserve Ags for prolonged periods of time and on stimulation show strong induction of both MHC class I and II, which explains their efficient activation of both CD4+ and CD8+ T cells. Furthermore, pDCs cross-present soluble and cell-associated tumor Ags to cytotoxic T lymphocytes equally well as BDCA3+ mDCs. These findings, and the fact that pDCs outnumber BDCA3+ mDCs, both in peripheral blood and lymph nodes, together with their potent IFN-I production, known to activate both components of the innate and adaptive immune system, put human pDCs forward as potent activators of CD8+ T cells in antitumor responses. Our findings may therefore have important consequences for the development of antitumor immunotherapy.

scholarly journals SOCS-3 Is Tyrosine Phosphorylated in Response to Interleukin-2 and Suppresses STAT5 Phosphorylation and Lymphocyte Proliferation

1999 ◽  
Vol 19 (7) ◽  
pp. 4980-4988 ◽  
Author(s):  
Solomon J. Cohney ◽  
David Sanden ◽  
Nicholas A. Cacalano ◽  
Akihiko Yoshimura ◽  
Alice Mui ◽  
...  
Keyword(s):  
T Cells ◽  
Tyrosine Phosphorylation ◽  
Human Peripheral Blood ◽  
Interleukin 2 ◽  
Peripheral Blood Lymphocytes ◽  
Cytokine Signaling ◽  
Socs Proteins ◽  
T Cell Lines ◽  
Receptor Beta

ABSTRACT Members of the recently discovered SOCS/CIS/SSI family have been proposed as regulators of cytokine signaling, and while targets and mechanisms have been suggested for some family members, the precise role of these proteins remains to be defined. To date no SOCS proteins have been specifically implicated in interleukin-2 (IL-2) signaling in T cells. Here we report SOCS-3 expression in response to IL-2 in both T-cell lines and human peripheral blood lymphocytes. SOCS-3 protein was detectable as early as 30 min following IL-2 stimulation, while CIS was seen only at low levels after 2 h. Unlike CIS, SOCS-3 was rapidly tyrosine phosphorylated in response to IL-2. Tyrosine phosphorylation of SOCS-3 was observed upon coexpression with Jak1 and Jak2 but only weakly with Jak3. In these experiments, SOCS-3 associated with Jak1 and inhibited Jak1 phosphorylation, and this inhibition was markedly enhanced by the presence of IL-2 receptor beta chain (IL-2Rβ). Moreover, following IL-2 stimulation of T cells, SOCS-3 was able to interact with the IL-2 receptor complex, and in particular tyrosine phosphorylated Jak1 and IL-2Rβ. Additionally, in lymphocytes expressing SOCS-3 but not CIS, IL-2-induced tyrosine phosphorylation of STAT5b was markedly reduced, while there was only a weak effect on IL-3-mediated STAT5b tyrosine phosphorylation. Finally, proliferation induced by both IL-2- and IL-3 was significantly inhibited in the presence of SOCS-3. The findings suggest that when SOCS-3 is rapidly induced by IL-2 in T cells, it acts to inhibit IL-2 responses in a classical negative feedback loop.

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