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.

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 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 Activation of natural killer cells via the p75 interleukin 2 receptor.

1989 ◽  
Vol 170 (1) ◽  
pp. 291-296 ◽  
Author(s):  
J H Phillips ◽  
T Takeshita ◽  
K Sugamura ◽  
L L Lanier
Keyword(s):  
Natural Killer Cells ◽  
Nk Cells ◽  
B Lymphocytes ◽  
Peripheral Blood ◽  
Cell Activation ◽  
Nk Cell ◽  
Human Peripheral Blood ◽  
Interleukin 2 ◽  
Maximal Inhibition ◽  
Activation Antigen

The IL-2R is composed of at least two subunits, the p55 (CD25/Tac) and p75 glycoproteins. The p75 IL-2R is expressed preferentially on resting human peripheral blood NK cells, but is not detected on substantial proportions of T and B lymphocytes, monocytes, or granulocytes. Anti-p75 IL-2R mAb substantially inhibits the early events associated with NK cell activation by IL-2, including inhibition of cytotoxic activity and induction of the CD69 early activation antigen. While anti-p55 IL-2R mAb alone failed to substantially inhibit the initial events of IL-2 stimulation, maximal inhibition of IL-2-induced cytotoxicity and proliferation was achieved by combining both anti-p55 IL-2R and anti-p75 IL-2R. Collectively, results from the present studies directly implicate the p75 IL-2R as the structure predominantly responsible for IL-2 activation of NK cells.

scholarly journals NK cells and CD8+ T cells cooperate to improve therapeutic responses in melanoma treated with interleukin-2 (IL-2) and CTLA-4 blockade

2015 ◽  
Vol 3 (1) ◽  
Author(s):  
Frederick J Kohlhapp ◽  
Joseph R Broucek ◽  
Tasha Hughes ◽  
Erica J Huelsmann ◽  
Jevgenijs Lusciks ◽  
...  
Keyword(s):  
T Cells ◽  
Nk Cells ◽  
Cd8 T Cells ◽  
Interleukin 2 ◽  
Therapeutic Responses

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.

Cytotoxic CD4+ T cells use granulysin to kill Cryptococcus neoformans, and activation of this pathway is defective in HIV patients

Blood ◽  
2006 ◽  
Vol 109 (5) ◽  
pp. 2049-2057 ◽  
Author(s):  
Chun Fu Zheng ◽  
Ling Ling Ma ◽  
Gareth J. Jones ◽  
M. John Gill ◽  
Alan M. Krensky ◽  
...  
Keyword(s):  
T Cells ◽  
Nk Cells ◽  
Cryptococcus Neoformans ◽  
Cd8 T Cells ◽  
Peripheral Blood ◽  
Cd4 T Cells ◽  
Peripheral Blood Lymphocytes ◽  
Effector Molecule ◽  
Microbicidal Activity ◽  
Anticryptococcal Activity

AbstractAn important mechanism of host defense to Cryptococcus neoformans involves the direct microbicidal activity of lymphocytes. The importance of CD4+ T cells is illustrated by the incidence of this infection in the acquired immunodeficiency syndrome (AIDS) patients; however, the relative activity of microbicidal CD4+ T cells compared with CD8+ T cells and natural killer (NK) cells has not been established. Further, although NK cells and CD8+ T cells use perforin or granulysin, respectively, to kill C neoformans, the effector molecule used by CD4+ T cells is not known. Experiments demonstrated that IL-2–activated peripheral blood lymphocytes from healthy adults acquire anticryptococcal activity, and surprisingly, that CD4+ T cells had the most profound effect on this activity. Using SrCl2induced degranulation and siRNA knockdown, granulysin was shown to be the effector molecule. Although activation by anti–CD3 + IL-2 resulted in the additional expression of perforin, this did not improve the anticryptococcal activity. Cryptococcal killing by CD4+ T cells was defective in human immunodeficiency virus (HIV)–infected patients due to dysregulated granulysin and perforin production in response to IL-2 or anti–CD3 + IL-2. In conclusion, CD4+ T cells are the major subset of cells responsible for killing C neoformans in peripheral blood. These cells use granulysin as the effector molecule, and priming is dysregulated in HIV-infected patients, which results in defective microbicidal activity.

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
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