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Functional inactivation in the whole population of human V gamma 9/V delta 2 T lymphocytes induced by a nonpeptidic antagonist.

Bürk MR, Carena I, Donda A, Mariani F, Mori L, De Libero G - J. Exp. Med. (1997)

Bottom Line: We report that one of these ligands, 2,3-diphosphoglyceric acid (DPG), which induces expansion of V gamma 9/V delta T cells ex vivo, antagonizes the same cell population after repetitive activation.These findings show that TCR antagonism is a general phenomenon of T cells.However, in contrast to the clonal specificity of altered peptides antagonizing alpha beta T cells, all the tested V gamma 9/V delta 2 polyclonal cell lines and clones become unresponsive, a fact that may be relevant for the regulation of their response in vivo.

View Article: PubMed Central - PubMed

Affiliation: Department of Research, University Hospital, Basel, Switzerland.

ABSTRACT
Nonpeptidic compounds stimulate human T cells bearing the TCR-gamma delta in the absence of major histocompatibility complex restriction. We report that one of these ligands, 2,3-diphosphoglyceric acid (DPG), which induces expansion of V gamma 9/V delta T cells ex vivo, antagonizes the same cell population after repetitive activation. Stimulation with DPG results in partial early protein tyrosine phosphorylation and a prolonged, but reversible, state of unresponsiveness to agonist ligands in V gamma 9/V delta 2, but not in other T cells. These findings show that TCR antagonism is a general phenomenon of T cells. However, in contrast to the clonal specificity of altered peptides antagonizing alpha beta T cells, all the tested V gamma 9/V delta 2 polyclonal cell lines and clones become unresponsive, a fact that may be relevant for the regulation of their response in vivo.

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Related in: MedlinePlus

Early signaling events, necessary for cytolytic function, are altered in cells made unresponsive by DPG. The figure shows results of killing of PHA-blasts by Vγ9/Vδ2 clone RNM.t.73 preincubated overnight  with medium (solid symbols) or DPG 1 mM (open symbols) in the presence  (squares) or absence (circles) of 100 μM IPP, at the indicated E/T ratios.
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Figure 4: Early signaling events, necessary for cytolytic function, are altered in cells made unresponsive by DPG. The figure shows results of killing of PHA-blasts by Vγ9/Vδ2 clone RNM.t.73 preincubated overnight with medium (solid symbols) or DPG 1 mM (open symbols) in the presence (squares) or absence (circles) of 100 μM IPP, at the indicated E/T ratios.

Mentions: Proliferation and lymphokine release both require nuclear gene activation. To study whether effects induced by earlier signaling events are altered by DPG, we performed cytotoxicity assays. IPP stimulates cytotoxic Vγ9/Vδ2 cells to kill target cells at low E/T ratios; however, IPP does not trigger killing by the same cells preincubated with DPG (Fig. 4). These results suggest that in unresponsive cells, not only late events, but also earlier signaling events leading to cytotoxic activity are affected.


Functional inactivation in the whole population of human V gamma 9/V delta 2 T lymphocytes induced by a nonpeptidic antagonist.

Bürk MR, Carena I, Donda A, Mariani F, Mori L, De Libero G - J. Exp. Med. (1997)

Early signaling events, necessary for cytolytic function, are altered in cells made unresponsive by DPG. The figure shows results of killing of PHA-blasts by Vγ9/Vδ2 clone RNM.t.73 preincubated overnight  with medium (solid symbols) or DPG 1 mM (open symbols) in the presence  (squares) or absence (circles) of 100 μM IPP, at the indicated E/T ratios.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2196105&req=5

Figure 4: Early signaling events, necessary for cytolytic function, are altered in cells made unresponsive by DPG. The figure shows results of killing of PHA-blasts by Vγ9/Vδ2 clone RNM.t.73 preincubated overnight with medium (solid symbols) or DPG 1 mM (open symbols) in the presence (squares) or absence (circles) of 100 μM IPP, at the indicated E/T ratios.
Mentions: Proliferation and lymphokine release both require nuclear gene activation. To study whether effects induced by earlier signaling events are altered by DPG, we performed cytotoxicity assays. IPP stimulates cytotoxic Vγ9/Vδ2 cells to kill target cells at low E/T ratios; however, IPP does not trigger killing by the same cells preincubated with DPG (Fig. 4). These results suggest that in unresponsive cells, not only late events, but also earlier signaling events leading to cytotoxic activity are affected.

Bottom Line: We report that one of these ligands, 2,3-diphosphoglyceric acid (DPG), which induces expansion of V gamma 9/V delta T cells ex vivo, antagonizes the same cell population after repetitive activation.These findings show that TCR antagonism is a general phenomenon of T cells.However, in contrast to the clonal specificity of altered peptides antagonizing alpha beta T cells, all the tested V gamma 9/V delta 2 polyclonal cell lines and clones become unresponsive, a fact that may be relevant for the regulation of their response in vivo.

View Article: PubMed Central - PubMed

Affiliation: Department of Research, University Hospital, Basel, Switzerland.

ABSTRACT
Nonpeptidic compounds stimulate human T cells bearing the TCR-gamma delta in the absence of major histocompatibility complex restriction. We report that one of these ligands, 2,3-diphosphoglyceric acid (DPG), which induces expansion of V gamma 9/V delta T cells ex vivo, antagonizes the same cell population after repetitive activation. Stimulation with DPG results in partial early protein tyrosine phosphorylation and a prolonged, but reversible, state of unresponsiveness to agonist ligands in V gamma 9/V delta 2, but not in other T cells. These findings show that TCR antagonism is a general phenomenon of T cells. However, in contrast to the clonal specificity of altered peptides antagonizing alpha beta T cells, all the tested V gamma 9/V delta 2 polyclonal cell lines and clones become unresponsive, a fact that may be relevant for the regulation of their response in vivo.

Show MeSH
Related in: MedlinePlus