T-cell receptor antagonist modifies cytokine secretion profile of naive CD4+ T cells and their differentiation into type-1 and type-2 helper T cells

2005 ◽  
Vol 96 (1) ◽  
pp. 39-45 ◽  
Author(s):  
Rumi Takato-Kaji ◽  
Mamoru Totsuka ◽  
Wataru Ise ◽  
Megumi Nishikawa ◽  
Satoshi Hachimura ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Receptor Antagonist ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Helper T Cells ◽  
Secretion Profile ◽  
Cytokine Secretion Profile

scholarly journals Granzyme B Is Critical for T Cell Receptor-Induced Cell Death of Type 2 Helper T Cells

Immunity ◽  
2006 ◽  
Vol 25 (2) ◽  
pp. 237-247 ◽  
Author(s):  
Satish Devadas ◽  
Jyoti Das ◽  
Catherine Liu ◽  
Liying Zhang ◽  
Arthur I. Roberts ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Death ◽  
T Cell ◽  
T Cell Receptor ◽  
Granzyme B ◽  
Cell Receptor ◽  
Helper T Cells

scholarly journals In Vivo Selection of T-Cell Receptor Junctional Region Sequences by HLA-A2 Human T-Cell Lymphotropic Virus Type 1 Tax11-19 Peptide Complexes

2001 ◽  
Vol 75 (2) ◽  
pp. 1065-1071 ◽  
Author(s):  
Mineki Saito ◽  
Graham P. Taylor ◽  
Akiko Saito ◽  
Yoshitaka Furukawa ◽  
Koichiro Usuku ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Virus Type ◽  
Cell Receptor ◽  
Antigen Specificity ◽  
Human T Cell ◽  
Cdr3 Region

ABSTRACT Using HLA-peptide tetrameric complexes, we isolated human T-cell lymphotrophic virus type 1 Tax peptide-specific CD8+ T cells ex vivo. Antigen-specific amino acid motifs were identified in the T-cell receptor Vβ CDR3 region of clonally expanded CD8+ T cells. This result directly confirms the importance of the CDR3 region in determining the antigen specificity in vivo.

scholarly journals T-cell-receptor signalling in inositol 1,4,5-trisphosphate receptor (IP3R) type-1-deficient mice: is IP3R type 1 essential for T-cell-receptor signalling?

1998 ◽  
Vol 333 (3) ◽  
pp. 615-619 ◽  
Author(s):  
Junji HIROTA ◽  
Masashi BABA ◽  
Mineo MATSUMOTO ◽  
Teiichi FURUICHI ◽  
Kiyoshi TAKATSU ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Line ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Cell Phenotype ◽  
Receptor Signalling ◽  
Inositol 1,4,5 Trisphosphate ◽  
Trisphosphate Receptor

Stimulation of T-cells via the T-cell receptor (TCR) complex is accompanied by an increase in intracellular Ca2+ concentration ([Ca2+]i). Recently, it was reported that a stable transformant of the human T-cell line, Jurkat, expressing an antisense cDNA construct of inositol 1,4,5-trisphosphate receptor (IP3R) type 1 (IP3R1), failed to demonstrate increased [Ca2+]i or interleukin-2 production after TCR stimulation and was also resistant to apoptotic stimuli. This cell line lacked IP3R1 expression, but expressed the type-2 and -3 receptors, IP3R2 and IP3R3 respectively [Jayaraman, Ondriasova, Ondrias, Harnick and Marks (1995) Proc. Natl. Acad. Sci. U.S.A. 92, 6007–6011, and Jayaraman and Marks (1997) Mol. Cell. Biol. 17, 3005–3012]. The authors concluded that IP3R1 is essential for TCR signalling and suggested that Ca2+ release via IP3R1 is a critical mediator of apoptosis. To establish whether a loss of IP3R1 function in T-cells occurred in vivo and in vitro, we investigated Ca2+ signalling after TCR stimulation and the properties of T-cells using IP3R1-deficient (IP3R1-/-) mice. As IP3R1-/- mice die at weaning, we transplanted bone marrow cells of IP3R1-/- mice into irradiated wild-type mice. Western blot analysis showed that the recipient IP3R1-containing (IP3R1+/+) lymphocytes were replaced by the donor IP3R1-/- lymphocytes after transplantation and that expression of IP3R2 and IP3R3 was unaltered. In contrast with the previous reports, T-cells lacking IP3R1 were able to mobilize Ca2+ from intracellular Ca2+ stores after stimulation via the TCR. We observed no significant differences between IP3R1+/+ and IP3R1-/- T-cells in terms of the number of thymocytes and splenocytes, the proportion of the T-cell phenotype, proliferative response to anti-CD3 monoclonal antibody (mAb) stimulation and cell viability. Therefore IP3R1 is not essential for T-cell development and function.

scholarly journals Extent of T cell receptor ligation can determine the functional differentiation of naive CD4+ T cells.

1995 ◽  
Vol 182 (5) ◽  
pp. 1591-1596 ◽  
Author(s):  
S Constant ◽  
C Pfeiffer ◽  
A Woodard ◽  
T Pasqualini ◽  
K Bottomly
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cd4 T Cells ◽  
Cell Receptor ◽  
Functional Differentiation ◽  
Interleukin 4 ◽  
Cell Mediated Immunity ◽  
Receptor Ligation

Naive CD4+ T cells can differentiate into cells predominantly involved in humoral immunity, known as T helper type 2 cells (Th2), or cells involved in cell-mediated immunity, known as Th1 cells. In this report, we show that priming of CD4+ T cells bearing a transgene-encoded T cell receptor can lead to differentiation into Th1-like cells producing abundant interferon gamma when the cells are exposed to high antigen doses, while low doses of the same peptide induce cells with the same T cell receptor to differentiate into Th2-like cells producing abundant interleukin 4. Thus antigen dose is one factor that can control the differentiation fate of a naive CD4+ T cell.

scholarly journals Inhibition of T-Cell Receptor Signal Transduction and Viral Expression by the Linker for Activation of T Cells-Interacting p12I Protein of Human T-Cell Leukemia/Lymphoma Virus Type 1

2007 ◽  
Vol 81 (17) ◽  
pp. 9088-9099 ◽  
Author(s):  
Risaku Fukumoto ◽  
Miroslav Dundr ◽  
Christophe Nicot ◽  
Anthony Adams ◽  
Valerio W. Valeri ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Virus Type ◽  
Calcium Release ◽  
Cell Receptor ◽  
Cell Leukemia ◽  
Viral Expression ◽  
Human T Cell

ABSTRACT The p12I protein of human T-cell leukemia/lymphoma virus type 1 (HTLV-1) is a small oncoprotein that increases calcium release following protein kinase C activation by phorbol myristate acetate, and importantly, this effect is linker for activation of T cells (LAT) independent. Here, we demonstrate that p12I inhibits the phosphorylation of LAT, Vav, and phospholipase C-γ1 and decreases NFAT (nuclear factor of activated T cells) activation upon engagement of the T-cell receptor (TCR) with anti-CD3 antibody. Furthermore, we demonstrate that p12I localizes to membrane lipid rafts and, upon engagement of the TCR, relocalizes to the interface between T cells and antigen-presenting cells, defined as the immunological synapse. A p12I knockout molecular clone of HTLV-1 expresses more virus upon antigen stimulation than the isogenic wild type, suggesting that, by decreasing T-cell responsiveness, p12I curtails viral expression. Thus, p12I has contrasting effects on TCR signaling: it down-regulates TCR in a LAT-dependent manner on one hand, and on the other, it increases calcium release in a LAT-independent manner. The negative regulation of T-cell activation by p12I may have evolved to minimize immune recognition of infected CD4+ T cells, to impair the function of infected cytotoxic CD8+ T cells, and to favor viral persistence in the infected host.

scholarly journals T-Cell Receptor-Mediated Anergy of a Human Immunodeficiency Virus (HIV) gp120-Specific CD4+ Cytotoxic T-Cell Clone, Induced by a Natural HIV Type 1 Variant Peptide

2000 ◽  
Vol 74 (5) ◽  
pp. 2121-2130 ◽  
Author(s):  
Latifa Bouhdoud ◽  
Patricia Villain ◽  
Abderrazzak Merzouki ◽  
Maximilian Arella ◽  
Clément Couture
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Cytotoxic T Cell ◽  
Ctl Response ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) infection triggers a cytotoxic T-lymphocyte (CTL) response mediated by CD8+ and perhaps CD4+ CTLs. The mechanisms by which HIV-1 escapes from this CTL response are only beginning to be understood. However, it is already clear that the extreme genetic variability of the virus is a major contributing factor. Because of the well-known ability of altered peptide ligands (APL) to induce a T-cell receptor (TCR)-mediated anergic state in CD4+ helper T cells, we investigated the effects of HIV-1 sequence variations on the proliferation and cytotoxic activation of a human CD4+ CTL clone (Een217) specific for an epitope composed of amino acids 410 to 429 of HIV-1 gp120. We report that a natural variant of this epitope induced a functional anergic state rendering the T cells unable to respond to their antigenic ligand and preventing the proliferation and cytotoxic activation normally induced by the original antigenic peptide. Furthermore, the stimulation of Een217 cells with this APL generated altered TCR-proximal signaling events that have been associated with the induction of T-cell anergy in CD4+ T cells. Importantly, the APL-induced anergic state of the Een217 T cells could be prevented by the addition of interleukin 2, which restored their ability to respond to their nominal antigen. Our data therefore suggest that HIV-1 variants can induce a state of anergy in HIV-specific CD4+ CTLs. Such a mechanism may allow a viral variant to not only escape the CTL response but also facilitate the persistence of other viral strains that may otherwise be recognized and eliminated by HIV-specific CTLs.

Multiple cis-acting elements in the human immunodeficiency virus type 2 enhancer mediate the response to T-cell receptor stimulation by antigen in a T-cell hybridoma line

Blood ◽  
1994 ◽  
Vol 83 (7) ◽  
pp. 1839-1846
Author(s):  
MC Hannibal ◽  
DM Markovitz ◽  
GJ Nabel
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Human Immunodeficiency Virus Type ◽  
Antigen Receptor ◽  
Cell Receptor ◽  
Regulatory Elements ◽  
Immunodeficiency Virus

Transcription directed by the human immunodeficiency virus type 2 long terminal repeat (HIV-2 LTR) responds to T-cell antigen receptor signaling. Agents that stimulate T-cell signaling pathways activated by the antigen receptor, such as phorbol ester, plant lectin, or anti-CD3 antibody treatment, have been shown to increase transcription directed by the HIV-2 LTR. In this study, we examine the activation of the HIV-2 LTR in T cells stimulated with the physiologic ligand of the T-cell receptor, antigenic peptide presented by a major histocompatibility molecule. HIV-2 reporter plasmids were transfected into the antigen- specific T-cell hybridoma, 2B4.11, where they responded to antigen- dependent activation. This antigen-mediated transcriptional activation of the HIV-2 enhancer required the presence of at least four regulatory elements in the HIV-2 enhancer, including two purine boxes, PuB1 and PuB2, an AP-1/CREB-like element (pets), and kappa B. This finding suggests that signals emanating from the antigen receptor act coordinately on a set of transcription factors that bind to conserved HIV-2 regulatory elements. Despite differences in the organization of potentially related enhancer elements in HIV-2 and IL-2, these enhancers exploit a similar signal transduction pathway to induce gene expression in antigen-activated T cells.

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