Eliciting Cytotoxic T-lymphocyte Responses to HIV by Human Dendrocyte In Vitro T-cell Activation with Synthetic Peptide-containing Microspheres

2014 ◽  
Vol 30 (S1) ◽  
pp. A243-A244
Author(s):  
Sarah S. Killingbeck ◽  
C V. Herst ◽  
Craig Rouskey ◽  
R M. Rubsamen
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
T Lymphocyte ◽  
Synthetic Peptide ◽  
Cell Activation ◽  
Cytotoxic T Lymphocyte ◽  
Lymphocyte Responses

Cytotoxic T-lymphocyte antigen-4 haplotypes and T cell activation in irritable bowel syndrome

2007 ◽  
Vol 45 (08) ◽  
Author(s):  
T Liebregts ◽  
B Adam ◽  
C Bredack ◽  
S Lester ◽  
S Downie-Doyle ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
T Cell ◽  
T Cell Activation ◽  
T Lymphocyte ◽  
Cell Activation ◽  
Cytotoxic T Lymphocyte ◽  
Lymphocyte Antigen ◽  
Irritable Bowel

scholarly journals Cytotoxic T Lymphocyte Antigen 4 (CTLA4) Blockade Accelerates the Acute Rejection of Cardiac Allografts in CD28-deficient Mice: CTLA4 Can Function Independently of CD28

1998 ◽  
Vol 188 (1) ◽  
pp. 199-204 ◽  
Author(s):  
Hua Lin ◽  
Jeffrey C. Rathmell ◽  
Gary S. Gray ◽  
Craig B. Thompson ◽  
Jeffrey M. Leiden ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
T Lymphocyte ◽  
Graft Rejection ◽  
Allograft Rejection ◽  
Cell Activation ◽  
Cytotoxic T Lymphocyte ◽  
Wild Type ◽  
Lymphocyte Antigen ◽  
Deficient Mice

Cytotoxic T lymphocyte antigen 4 (CTLA4) appears to negatively regulate T cell activation. One mechanism by which CTLA4 might antagonize T cell function is through inhibition of CD28 signaling by competing for their shared ligands B7-1 and B7-2. In addition, CTLA4 ligation could initiate a signaling cascade that inhibits T cell activation. To address whether CTLA4 could inhibit immune responses in the absence of CD28, rejection of heart allografts was studied in CD28-deficient mice. H-2q hearts were transplanted into allogeneic wild-type or CD28-deficient mice (H-2b). Graft rejection was delayed in CD28-deficient compared with wild-type mice. Treatment of wild-type recipients with CTLA4-immunoglobulin (Ig), or with anti–B7-1 plus anti–B7-2 mAbs significantly prolonged allograft survival. In contrast, treatment of CD28-deficient mice with CTLA4-Ig, anti–B7-1 plus anti–B7-2 mAbs, or a blocking anti-CTLA4 mAb induced acceleration of allograft rejection. This increased rate of graft rejection was associated with more severe mononuclear cell infiltration and enhanced levels of IFN-γ and IL-6 transcripts in donor hearts of untreated wild-type and CTLA4-Ig– or anti-CTLA4 mAb–treated CD28-deficient mice. Thus, the negative regulatory role of CTLA4 extends beyond its potential ability to prevent CD28 activation through ligand competition. Even in the absence of CD28, CTLA4 plays an inhibitory role in the regulation of allograft rejection.

scholarly journals Ligation of Cytotoxic T Lymphocyte Antigen-4 to T Cell Receptor Inhibits T Cell Activation and Directs Differentiation into Foxp3+Regulatory T Cells

2012 ◽  
Vol 287 (14) ◽  
pp. 11098-11107 ◽  
Author(s):  
Jozsef Karman ◽  
Ji-Lei Jiang ◽  
Nathan Gumlaw ◽  
Hongmei Zhao ◽  
Juanita Campos-Rivera ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
T Cell Receptor ◽  
T Cell Activation ◽  
T Lymphocyte ◽  
Cell Activation ◽  
Cytotoxic T Lymphocyte ◽  
Cell Receptor ◽  
Lymphocyte Antigen

scholarly journals Lack of a role for transforming growth factor-  in cytotoxic T lymphocyte antigen-4-mediated inhibition of T cell activation

2001 ◽  
Vol 98 (5) ◽  
pp. 2587-2592 ◽  
Author(s):  
T. J. Sullivan ◽  
J. J. Letterio ◽  
A. van Elsas ◽  
M. Mamura ◽  
J. van Amelsfort ◽  
...  
Keyword(s):  
T Cell ◽  
Growth Factor ◽  
T Cell Activation ◽  
T Lymphocyte ◽  
Cell Activation ◽  
Transforming Growth Factor ◽  
Cytotoxic T Lymphocyte ◽  
Lymphocyte Antigen

scholarly journals Cytotoxic T Lymphocyte Antigen 4 (Ctla-4) Engagement Delivers an Inhibitory Signal through the Membrane-Proximal Region in the Absence of the Tyrosine Motif in the Cytoplasmic Tail

1999 ◽  
Vol 190 (6) ◽  
pp. 765-774 ◽  
Author(s):  
Chiaki Nakaseko ◽  
Shoichiro Miyatake ◽  
Tomohiko Iida ◽  
Satoru Hara ◽  
Ryo Abe ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
T Lymphocyte ◽  
Cell Activation ◽  
Cytotoxic T Lymphocyte ◽  
Interleukin 2 ◽  
Cytoplasmic Tail ◽  
Proximal Region ◽  
Lymphocyte Antigen ◽  
Membrane Proximal Region

Cytotoxic T lymphocyte antigen 4 (CTLA-4) is a T cell costimulation receptor that delivers inhibitory signals upon activation. Although the tyrosine-based motif (165YVKM) within its cytoplasmic tail has been shown to associate in vitro with Src homology 2 domain–containing tyrosine phosphatase (SHP-2) and phosphatidylinositol 3 kinase upon phosphorylation, the mechanism of negative signaling remains unclear. Here, we report a new mechanism of negative signaling based on the analysis of murine T cell clones transfected with various mutants of CTLA-4. Upon T cell activation by cross-linking with anti-CD3 and anti-CD28 antibodies, CTLA-4 engagement inhibited both proliferation and interleukin 2 production in tyrosine mutants as well as in wild-type CTLA-4 transfectants. Furthermore, the mutant CTLA-4 lacking most of the cytoplasmic region strongly suppressed interleukin 2 production as well. These data suggest that negative signals by CTLA-4 could be mediated through the membrane-proximal region of CTLA-4 but not through the YVKM motif and that the association of CTLA-4 with SHP-2 is not required for CTLA-4–mediated suppression of T cell activation.

scholarly journals B7-1 or B7-2 Is Required to Produce the Lymphoproliferative Phenotype in Mice Lacking Cytotoxic T Lymphocyte–associated Antigen 4 (CTLA-4)

1999 ◽  
Vol 189 (2) ◽  
pp. 435-440 ◽  
Author(s):  
Didier A. Mandelbrot ◽  
Alexander J. McAdam ◽  
Arlene H. Sharpe
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
T Lymphocyte ◽  
Cell Activation ◽  
Cytotoxic T Lymphocyte ◽  
Lymphocyte Activation ◽  
Lymphoproliferative Disease ◽  
Inhibitory Function ◽  
B7 Molecules

The costimulatory molecules B7-1 and B7-2 regulate T lymphocyte activation by delivering activating signals through CD28 and inhibitory signals through cytotoxic T lymphocyte–associated antigen 4 (CTLA-4). The importance of CTLA-4–mediated inhibition was demonstrated by the uncontrolled T cell activation and lymphoproliferative disease that develops in CTLA-4–deficient (−/−) mice. To examine the role of B7 signaling in the activation of CTLA-4–deficient T cells, we bred CTLA-4−/− mice with mice lacking B7-1, B7-2, or both B7 molecules. The CTLA-4/B7-1−/− and the CTLA-4/B7-2−/− mice develop lymphoproliferation and enhanced T cell activation. Mice lacking CTLA-4, B7-1, and B7-2 have a normal life-span, and do not have lymphocytic infiltrates in any organs, or increased T cell activation. Therefore, the two B7 molecules have overlapping functions, since either B7-1 or B7-2 alone can cause the CTLA-4−/− phenotype. Elimination of both B7-1 and B7-2 from the CTLA-4– deficient mouse abrogates the lymphocyte activation and disease, and does not reveal evidence for additional stimulatory CD28 ligands. The CTLA-4−/− phenotype can be reproduced with anti-CD28 antibody in mice lacking CTLA-4, B7-1, and B7-2, but wild-type mice are unaffected by the same treatment. This suggests that the inhibitory function of CTLA-4 can overcome strong CD28-mediated signaling in vivo.

Abatacept (Cytotoxic T Lymphocyte Antigen 4-Fragment Crystallizable) Reduces Allergic Inflammation of Ovalbumin-Sensitized Mice.

2022 ◽  
pp. 194589242110723
Author(s):  
Jaein Chung ◽  
Mi-Ra Choi ◽  
Min Gyu Kim ◽  
Soo Kyoung Park ◽  
Yong Min Kim
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
T Lymphocyte ◽  
Cell Activation ◽  
Cytotoxic T Lymphocyte ◽  
Allergic Inflammation ◽  
Control Group ◽  
Western Blot Assay ◽  
Lymphocyte Antigen ◽  
Cluster Of Differentiation

Background Abatacept (Aba) is a cytotoxic T-lymphocyte antigen-4 and fragment crystallizable fusion protein. Aba blocks B7/Cluster of differentiation 28 - cytotoxic T-lymphocyte antigen-4 costimulatory pathway, inhibits cluster of differentiation 4+ T-cell activation, and is used as an anti-inflammatory drug. Objectives We conducted this study to assess the effectiveness of Aba in the treatment of allergic rhinitis (AR) in a mouse model. Methods We divided 40 four-week-old BALB/c mice into four groups: control group ( n = 10), positive control group (AR, n = 10), Aba group (AR + Aba, n = 10), and dexamethasone group (AR + Dex, n = 10). Mice in each group were challenged intranasally with daily ovalbumin (OVA) administration. Episodes of sneezing and nose rubbing were counted. Mice were sacrificed on day 42 and cytokines were measured in nasal lavage fluid. Nasal mucosae of five mice from each group were used for reverse transcriptase-polymerase chain reaction and western blot assay. Samples were collected from five mice from each group for histological analysis. Results Symptoms of AR significantly improved in the AR + Aba and AR + Dex groups compared with the AR group. Fewer eosinophils and goblet cells were seen in the AR + Aba and AR + Dex groups compared with the AR group. Both the AR + Aba and AR + Dex groups showed a significant decrease in nasal T helper 2 cytokine levels, including interleukin (IL)-4, IL-5, IL-13 and T cell activation related IL-17A, and interferon gamma (IFN- γ). Total immunoglobulin (Ig) E and OVA-specific IgG1 levels were also significantly lower in the AR + Aba and AR + Dex groups. OVA-specific IgE level was also significantly lower in the AR + Aba than AR group. Conclusions Aba suppresses allergic inflammation and appears to be a good treatment for AR.

The CD28 family: a T-cell rheostat for therapeutic control of T-cell activation

Blood ◽  
2005 ◽  
Vol 105 (1) ◽  
pp. 13-21 ◽  
Author(s):  
James L. Riley ◽  
Carl H. June
Keyword(s):  
Immune Response ◽  
Clinical Trials ◽  
T Cell ◽  
T Cell Activation ◽  
T Lymphocyte ◽  
Cell Activation ◽  
Cytotoxic T Lymphocyte ◽  
Critical Role ◽  
Inducible Costimulator ◽  
The Status

Abstract The CD28 family of receptors (CD28, cytotoxic T-lymphocyte–associated antigen 4 [CTLA-4], inducible costimulator [ICOS], program death-1 [PD-1], and B- and T-lymphocyte attenuator [BTLA]) plays a critical role in controlling the adaptive arm of the immune response. While considerable information is available regarding CD28 and CTLA-4, the function of the more recently discovered members of the CD28 family is less well understood. This review will highlight recent findings regarding the CD28 family with special emphasis on effects the CD28 family has on immunopathology, the discovery of costimulatory antibodies with superagonist function, and the status of clinical trials using various strategies to augment or block T-cell costimulation.

scholarly journals Negative Regulation of T Cell Receptor–Lipid Raft Interaction by Cytotoxic T Lymphocyte–associated Antigen 4

2003 ◽  
Vol 197 (1) ◽  
pp. 129-135 ◽  
Author(s):  
Shunsuke Chikuma ◽  
John B. Imboden ◽  
Jeffrey A. Bluestone
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
T Cell Activation ◽  
T Lymphocyte ◽  
Cell Activation ◽  
Immunological Synapse ◽  
Cytotoxic T Lymphocyte ◽  
Cell Receptor ◽  
T Cell Signaling ◽  
Signaling Complex

Cytotoxic T lymphocyte–associated antigen 4 (CTLA-4) is an essential negative regulator of T cell activation. Recent evidence suggests that CTLA-4 association with the immunological synapse during contact with antigen-presenting cells is important for its inhibitory function. In the present study, we observed a direct interaction of CTLA-4 with the phosphorylated form of T cell receptor (TCR)ζ within the glycolipid-enriched microdomains associated with the T cell signaling complex. In this setting, CTLA-4 regulated the accumulation/retention of TCRζ in the signaling complex, as the lipid raft fractions from CTLA-4KO T cells contained significantly higher amounts of the TCR components when compared with wild-type littermates. In contrast, coligation of CTLA-4 with the TCR during T cell activation selectively decreased the amount of TCRζ that accumulated in the rafts. These results suggest that CTLA-4 functions to regulate T cell signaling by controlling TCR accumulation and/or retention within this a critical component of the immunological synapse.

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