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Expression of the transcription factor cKrox in peripheral CD8 T cells reveals substantial postthymic plasticity in CD4-CD8 lineage differentiation.

Jenkinson SR, Intlekofer AM, Sun G, Feigenbaum L, Reiner SL, Bosselut R - J. Exp. Med. (2007)

Bottom Line: It is, however, unclear whether the CD4-CD8 differentiation of postthymic T cells retains some level of plasticity or is stably maintained by mechanisms distinct from those that set lineage choice in the thymus.To address this issue, we examined if coreceptor or effector gene expression in mature CD8 T cells remains sensitive to the zinc finger transcription factor cKrox, which promotes CD4 and inhibits CD8 differentiation when expressed in thymocytes.These observations reveal a persistent degree of plasticity in CD4-CD8 differentiation in mature T cells.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

ABSTRACT
Most T cells belong to either of two lineages defined by the mutually exclusive expression of CD4 and CD8 coreceptors: CD4 T cells are major histocompatibility complex (MHC) II restricted and have helper function, whereas CD8 T cells are MHC I restricted and have cytotoxic function. The divergence between these two lineages occurs during intrathymic selection and is thought to be irreversible in mature T cells. It is, however, unclear whether the CD4-CD8 differentiation of postthymic T cells retains some level of plasticity or is stably maintained by mechanisms distinct from those that set lineage choice in the thymus. To address this issue, we examined if coreceptor or effector gene expression in mature CD8 T cells remains sensitive to the zinc finger transcription factor cKrox, which promotes CD4 and inhibits CD8 differentiation when expressed in thymocytes. We show that cKrox transduction into CD8 T cells inhibits their expression of CD8 and cytotoxic effector genes and impairs their cytotoxic activity, and that it promotes expression of helper-specific genes, although not of CD4 itself. These observations reveal a persistent degree of plasticity in CD4-CD8 differentiation in mature T cells.

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Related in: MedlinePlus

cKrox promotes expression of helper-specific genes by CD8 T cells. (A) Lymph node cells transduced with cKrox or control retrovirus were analyzed by intracellular staining and flow cytometry for IL-2 production. Overlaid histograms gated on CD8+GFP+ (left) or CD4+GFP+ (right) cells show IL-2 expression after restimulation with PMA and ionomycin (filled) or without restimulation (dotted line). (B) mRNA expression of Gata3 and IL-4 was analyzed by RT-PCR in cKrox- or control-transduced CD8 cells and in untransduced CD4 cells, all activated in type 2 conditions. Results are relative to control-transduced CD8 cells (arbitrarily set to 1). Results in each panel are representative of three experiments.
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fig4: cKrox promotes expression of helper-specific genes by CD8 T cells. (A) Lymph node cells transduced with cKrox or control retrovirus were analyzed by intracellular staining and flow cytometry for IL-2 production. Overlaid histograms gated on CD8+GFP+ (left) or CD4+GFP+ (right) cells show IL-2 expression after restimulation with PMA and ionomycin (filled) or without restimulation (dotted line). (B) mRNA expression of Gata3 and IL-4 was analyzed by RT-PCR in cKrox- or control-transduced CD8 cells and in untransduced CD4 cells, all activated in type 2 conditions. Results are relative to control-transduced CD8 cells (arbitrarily set to 1). Results in each panel are representative of three experiments.

Mentions: As cKrox represses CD8 lineage genes, we examined if, conversely, it would induce helper-type gene expression. We first assessed its effect on IL-2, a cytokine produced by activated CD4 T cells independently of type 1 or 2 effector differentiation (6). Intracellular cytokine staining and flow cytometry showed that cKrox transduction into CD8 T cells promoted IL-2 production (Fig. 4 A). Another hallmark of CD4 cells is their high expression of Gata3, a transcription factor required for the production of type 2 cytokines such as IL-4 (20–22). cKrox transduction into CD8 cells cultured in type 2 conditions increased mRNA expression of Gata3 and of its target IL-4 (Fig. 4 B).


Expression of the transcription factor cKrox in peripheral CD8 T cells reveals substantial postthymic plasticity in CD4-CD8 lineage differentiation.

Jenkinson SR, Intlekofer AM, Sun G, Feigenbaum L, Reiner SL, Bosselut R - J. Exp. Med. (2007)

cKrox promotes expression of helper-specific genes by CD8 T cells. (A) Lymph node cells transduced with cKrox or control retrovirus were analyzed by intracellular staining and flow cytometry for IL-2 production. Overlaid histograms gated on CD8+GFP+ (left) or CD4+GFP+ (right) cells show IL-2 expression after restimulation with PMA and ionomycin (filled) or without restimulation (dotted line). (B) mRNA expression of Gata3 and IL-4 was analyzed by RT-PCR in cKrox- or control-transduced CD8 cells and in untransduced CD4 cells, all activated in type 2 conditions. Results are relative to control-transduced CD8 cells (arbitrarily set to 1). Results in each panel are representative of three experiments.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2118724&req=5

fig4: cKrox promotes expression of helper-specific genes by CD8 T cells. (A) Lymph node cells transduced with cKrox or control retrovirus were analyzed by intracellular staining and flow cytometry for IL-2 production. Overlaid histograms gated on CD8+GFP+ (left) or CD4+GFP+ (right) cells show IL-2 expression after restimulation with PMA and ionomycin (filled) or without restimulation (dotted line). (B) mRNA expression of Gata3 and IL-4 was analyzed by RT-PCR in cKrox- or control-transduced CD8 cells and in untransduced CD4 cells, all activated in type 2 conditions. Results are relative to control-transduced CD8 cells (arbitrarily set to 1). Results in each panel are representative of three experiments.
Mentions: As cKrox represses CD8 lineage genes, we examined if, conversely, it would induce helper-type gene expression. We first assessed its effect on IL-2, a cytokine produced by activated CD4 T cells independently of type 1 or 2 effector differentiation (6). Intracellular cytokine staining and flow cytometry showed that cKrox transduction into CD8 T cells promoted IL-2 production (Fig. 4 A). Another hallmark of CD4 cells is their high expression of Gata3, a transcription factor required for the production of type 2 cytokines such as IL-4 (20–22). cKrox transduction into CD8 cells cultured in type 2 conditions increased mRNA expression of Gata3 and of its target IL-4 (Fig. 4 B).

Bottom Line: It is, however, unclear whether the CD4-CD8 differentiation of postthymic T cells retains some level of plasticity or is stably maintained by mechanisms distinct from those that set lineage choice in the thymus.To address this issue, we examined if coreceptor or effector gene expression in mature CD8 T cells remains sensitive to the zinc finger transcription factor cKrox, which promotes CD4 and inhibits CD8 differentiation when expressed in thymocytes.These observations reveal a persistent degree of plasticity in CD4-CD8 differentiation in mature T cells.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

ABSTRACT
Most T cells belong to either of two lineages defined by the mutually exclusive expression of CD4 and CD8 coreceptors: CD4 T cells are major histocompatibility complex (MHC) II restricted and have helper function, whereas CD8 T cells are MHC I restricted and have cytotoxic function. The divergence between these two lineages occurs during intrathymic selection and is thought to be irreversible in mature T cells. It is, however, unclear whether the CD4-CD8 differentiation of postthymic T cells retains some level of plasticity or is stably maintained by mechanisms distinct from those that set lineage choice in the thymus. To address this issue, we examined if coreceptor or effector gene expression in mature CD8 T cells remains sensitive to the zinc finger transcription factor cKrox, which promotes CD4 and inhibits CD8 differentiation when expressed in thymocytes. We show that cKrox transduction into CD8 T cells inhibits their expression of CD8 and cytotoxic effector genes and impairs their cytotoxic activity, and that it promotes expression of helper-specific genes, although not of CD4 itself. These observations reveal a persistent degree of plasticity in CD4-CD8 differentiation in mature T cells.

Show MeSH
Related in: MedlinePlus