Proliferative properties of murine intestinal intraepithelial lymphocytes (IEL): IEL expressing TCRαβ or TCRτδ are largely unresponsive to proliferative signals mediated via conventional stimulation of the CD3-TCR complex

R. Lee Mosley, Michael Whetsell, John R. Klein

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Abstract

Murine intestinal intraepithelial lymphocytes (IEL) were studied for their capacity to proliferate in vitro following stimulation of the T cell receptor (TCR)-associated CD3ε molecule, or upon direct stimulation of the TCR complex itself. Although IEL consisted primarily of CD3+ T cells which included activated cytotoxicT lymphocytes as demonstrated in CD3- and TCR-mediated redirected cytotoxic assays, IEL displayed minimal proliferative responses following stimulation with anti-CD3, anti-TCRαβ or antl-TCRτδ monocional antibodies under soluble conditions, or under conditions which effect membrane cross-linking, including the addition of accessory cells toIEL cultures. The lack of proliferation induction could not be overcome by stimulation of IEL In the presence of T cell-dependent cytokines, phorbol ester, or interieukin-4. Moreover, unlike splenic T cells, stimulation of IEL failed to result In expression of interleukln-2 receptor, further demonstrating an Inability of IEL to respond to exogenous proliferatlve signals. This study Is the first to examine the proliferative potential of murine IEL following direct CD3 or TCR stimulation. The findings described here: (i) identify an important functional distinction between intestinal IEL and other peripheral αβ or τδ T cells which generally respond well to proliferative signals mediated through the CD3-TCR complex, and (ll) demonstrate that on murine IEL the CD3-TCR complex can discriminate signals of lytlc activityfrom those of cell proliferation.

Original languageEnglish (US)
Pages (from-to)563-569
Number of pages7
JournalInternational Immunology
Volume3
Issue number6
DOIs
StatePublished - Jun 1 1991

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T-cells
Lymphocytes
T-Cell Antigen Receptor
Receptor
T-Lymphocytes
Lymphocyte Activation
Phorbol Esters
Cytokines
Cell Culture
Cell Proliferation
Cell Culture Techniques
Cell proliferation
Accessories
Proliferation
Cell culture
Antibody
Antibodies
Linking
Membranes
Assays

Keywords

  • Intestinal T cells
  • Mucosal immunology
  • Signal transduction

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

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title = "Proliferative properties of murine intestinal intraepithelial lymphocytes (IEL): IEL expressing TCRαβ or TCRτδ are largely unresponsive to proliferative signals mediated via conventional stimulation of the CD3-TCR complex",
abstract = "Murine intestinal intraepithelial lymphocytes (IEL) were studied for their capacity to proliferate in vitro following stimulation of the T cell receptor (TCR)-associated CD3ε molecule, or upon direct stimulation of the TCR complex itself. Although IEL consisted primarily of CD3+ T cells which included activated cytotoxicT lymphocytes as demonstrated in CD3- and TCR-mediated redirected cytotoxic assays, IEL displayed minimal proliferative responses following stimulation with anti-CD3, anti-TCRαβ or antl-TCRτδ monocional antibodies under soluble conditions, or under conditions which effect membrane cross-linking, including the addition of accessory cells toIEL cultures. The lack of proliferation induction could not be overcome by stimulation of IEL In the presence of T cell-dependent cytokines, phorbol ester, or interieukin-4. Moreover, unlike splenic T cells, stimulation of IEL failed to result In expression of interleukln-2 receptor, further demonstrating an Inability of IEL to respond to exogenous proliferatlve signals. This study Is the first to examine the proliferative potential of murine IEL following direct CD3 or TCR stimulation. The findings described here: (i) identify an important functional distinction between intestinal IEL and other peripheral αβ or τδ T cells which generally respond well to proliferative signals mediated through the CD3-TCR complex, and (ll) demonstrate that on murine IEL the CD3-TCR complex can discriminate signals of lytlc activityfrom those of cell proliferation.",
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author = "Mosley, {R. Lee} and Michael Whetsell and Klein, {John R.}",
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T1 - Proliferative properties of murine intestinal intraepithelial lymphocytes (IEL)

T2 - IEL expressing TCRαβ or TCRτδ are largely unresponsive to proliferative signals mediated via conventional stimulation of the CD3-TCR complex

AU - Mosley, R. Lee

AU - Whetsell, Michael

AU - Klein, John R.

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N2 - Murine intestinal intraepithelial lymphocytes (IEL) were studied for their capacity to proliferate in vitro following stimulation of the T cell receptor (TCR)-associated CD3ε molecule, or upon direct stimulation of the TCR complex itself. Although IEL consisted primarily of CD3+ T cells which included activated cytotoxicT lymphocytes as demonstrated in CD3- and TCR-mediated redirected cytotoxic assays, IEL displayed minimal proliferative responses following stimulation with anti-CD3, anti-TCRαβ or antl-TCRτδ monocional antibodies under soluble conditions, or under conditions which effect membrane cross-linking, including the addition of accessory cells toIEL cultures. The lack of proliferation induction could not be overcome by stimulation of IEL In the presence of T cell-dependent cytokines, phorbol ester, or interieukin-4. Moreover, unlike splenic T cells, stimulation of IEL failed to result In expression of interleukln-2 receptor, further demonstrating an Inability of IEL to respond to exogenous proliferatlve signals. This study Is the first to examine the proliferative potential of murine IEL following direct CD3 or TCR stimulation. The findings described here: (i) identify an important functional distinction between intestinal IEL and other peripheral αβ or τδ T cells which generally respond well to proliferative signals mediated through the CD3-TCR complex, and (ll) demonstrate that on murine IEL the CD3-TCR complex can discriminate signals of lytlc activityfrom those of cell proliferation.

AB - Murine intestinal intraepithelial lymphocytes (IEL) were studied for their capacity to proliferate in vitro following stimulation of the T cell receptor (TCR)-associated CD3ε molecule, or upon direct stimulation of the TCR complex itself. Although IEL consisted primarily of CD3+ T cells which included activated cytotoxicT lymphocytes as demonstrated in CD3- and TCR-mediated redirected cytotoxic assays, IEL displayed minimal proliferative responses following stimulation with anti-CD3, anti-TCRαβ or antl-TCRτδ monocional antibodies under soluble conditions, or under conditions which effect membrane cross-linking, including the addition of accessory cells toIEL cultures. The lack of proliferation induction could not be overcome by stimulation of IEL In the presence of T cell-dependent cytokines, phorbol ester, or interieukin-4. Moreover, unlike splenic T cells, stimulation of IEL failed to result In expression of interleukln-2 receptor, further demonstrating an Inability of IEL to respond to exogenous proliferatlve signals. This study Is the first to examine the proliferative potential of murine IEL following direct CD3 or TCR stimulation. The findings described here: (i) identify an important functional distinction between intestinal IEL and other peripheral αβ or τδ T cells which generally respond well to proliferative signals mediated through the CD3-TCR complex, and (ll) demonstrate that on murine IEL the CD3-TCR complex can discriminate signals of lytlc activityfrom those of cell proliferation.

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