Streptococcus pyogenes –induced cutaneous lymphocyte antigen–positive T cell–dependent epidermal cell activation triggers T H 17 responses in patients with guttate psoriasis

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.

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Distinct cell surface ligands mediate T lymphocyte attachment and rolling on P and E selectin under physiological flow.

The Journal of Cell Biology ◽

10.1083/jcb.127.5.1485 ◽

1994 ◽

Vol 127 (5) ◽

pp. 1485-1495 ◽

Cited By ~ 99

Author(s):

R Alon ◽

H Rossiter ◽

X Wang ◽

T A Springer ◽

T S Kupper

Keyword(s):

T Cells ◽

T Cell ◽

T Lymphocytes ◽

Cell Surface ◽

Antigen Expression ◽

Lymphocyte Antigen ◽

Selectin Ligands ◽

Distinct Cell ◽

Cutaneous Lymphocyte Antigen

Memory T lymphocytes extravasate at sites of inflammation, but the mechanisms employed by these cells to initiate contact and tethering with endothelium are incompletely understood. An important part of leukocyte extravasation is the initiation of rolling adhesions on endothelial selectins; such events have been studied in monocytes and neutrophils but not lymphocytes. In this study, the potential of T lymphocytes to adhere and roll on endothelial selectins in vitro was investigated. We demonstrate that T cells can form tethers and rolling adhesions on P selectin and E selectin under physiologic flow conditions. Tethering and rolling on P selectin was independent of cell-surface cutaneous lymphocyte antigen (CLA) expression, which correlated strictly with the capacity of T cells to form rolling adhesions under flow on E selectin. T cell tethering to P selectin was abolished by selective removal of cell surface sialomucins by a P. haemolytica O-glycoprotease, while cutaneous lymphocyte antigen expression was unaffected. A sialomucin molecule identical or closely related to P selectin glycoprotein ligand-1 (PSGL-1), the major P selectin ligand on neutrophils and HL-60 cells, appears to be a major T cell ligand for P selectin. P selectin glycoprotein ligand-1 does not appear to support T cell rolling on E selectin. In turn, E selectin ligands do not appear to be associated with sialomucins. These data demonstrate the presence of structurally distinct ligands for P or E selectins on T cells, provide evidence that both ligands can be coexpressed on a single T cell, and mediate tethering and rolling on the respective selectins in a mutually exclusive fashion.

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

Journal of Biological Chemistry ◽

10.1074/jbc.m111.283705 ◽

2012 ◽

Vol 287 (14) ◽

pp. 11098-11107 ◽

Cited By ~ 16

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

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

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.051632398 ◽

2001 ◽

Vol 98 (5) ◽

pp. 2587-2592 ◽

Cited By ~ 39

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

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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

Journal of Experimental Medicine ◽

10.1084/jem.190.6.765 ◽

1999 ◽

Vol 190 (6) ◽

pp. 765-774 ◽

Cited By ~ 73

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.

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Faculty Opinions recommendation of Streptococcus induces circulating CLA(+) memory T-cell-dependent epidermal cell activation in psoriasis.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717967642.793467427 ◽

2012 ◽

Author(s):

Michelle Lowes ◽

Jamie Lynn Harden

Keyword(s):

T Cell ◽

Epidermal Cell ◽

Cell Activation ◽

Memory T Cell

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

American Journal of Rhinology and Allergy ◽

10.1177/19458924211072364 ◽

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.

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