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Restricted clonal expression of IL-2 by naive T cells reflects differential dynamic interactions with dendritic cells.

Hurez V, Saparov A, Tousson A, Fuller MJ, Kubo T, Oliver J, Weaver BT, Weaver CT - J. Exp. Med. (2003)

Bottom Line: T cells destined to produce IL-2 required prolonged interactions with DCs, whereas most T cells established only transient interactions with DCs and were activated, but did not express IL-2.Extended conjugation of T cells with DCs was not always sufficient to initiate IL-2 expression.Thus, there is intrinsic variability in clonal T cell populations that restricts IL-2 commitment, and prolonged engagement with mature DCs is necessary, but not sufficient, for IL-2 gene transcription.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, University of Alabama at Birmingham, AL 35294, USA.

ABSTRACT
Limited frequencies of T cells express IL-2 in primary antigenic responses, despite activation marker expression and proliferation by most clonal members. To define the basis for restricted IL-2 expression, a videomicroscopic system and IL-2 reporter transgenic model were used to characterize dendritic cell (DC)-T cell interactions. T cells destined to produce IL-2 required prolonged interactions with DCs, whereas most T cells established only transient interactions with DCs and were activated, but did not express IL-2. Extended conjugation of T cells with DCs was not always sufficient to initiate IL-2 expression. Thus, there is intrinsic variability in clonal T cell populations that restricts IL-2 commitment, and prolonged engagement with mature DCs is necessary, but not sufficient, for IL-2 gene transcription.

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Limited induction of IL-2+ cells is a consistent feature of the primary CD4 T cell response induced by distinct, mature DC populations. DC populations were as follows: splenic DCs purified from BALB/c mice, bone marrow-derived DCs (BM DCs), and a mature hybrid DC line (V-2 DC line). 5 × 105 CD4 T cells from DO11.IL-2P/GFP mice were incubated in culture wells with 1.5 × 105 DCs from each source with or without 10 μg/ml OVAp for 48 h. The frequency of CD4+, GFP+, and CD25+ cells was assessed by flow cytometry on the lymphoid gate.
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fig1: Limited induction of IL-2+ cells is a consistent feature of the primary CD4 T cell response induced by distinct, mature DC populations. DC populations were as follows: splenic DCs purified from BALB/c mice, bone marrow-derived DCs (BM DCs), and a mature hybrid DC line (V-2 DC line). 5 × 105 CD4 T cells from DO11.IL-2P/GFP mice were incubated in culture wells with 1.5 × 105 DCs from each source with or without 10 μg/ml OVAp for 48 h. The frequency of CD4+, GFP+, and CD25+ cells was assessed by flow cytometry on the lymphoid gate.

Mentions: Distinct populations of mature DCs were surveyed for their capacity to activate a clonal CD4 T cell response using the DO11.IL-2P/GFP transgenic model. Three populations of mature DCs were examined: (a) purified CD11c+ DCs isolated from spleen; (b) BM-derived mature DCs (24); and (c) the V-2 control DC hybrid line (25, 26). Naive CD4 T cells from DO11.IL-2P/GFP mice were incubated with DCs from each source and the frequency of IL-2/GFP+ cells was assessed 20 h after stimulation with or without OVA peptide (Fig. 1). In all cases, the frequency of GFP+ cells was less than one fourth of the CD4 T cell population (spleen DCs, 23.7%; BM DCs, 20.5%; and V-2 DC line, 20.9%). In contrast, 60–80% of CD4 T cells up-regulated CD25 irrespective of the type of DC used (Fig. 1). Thus, expression of IL-2/GFP by a limited subpopulation of antigen-activated naive T cells was a common feature of the clonal response, and was independent of the type of mature DC population used to present antigen.


Restricted clonal expression of IL-2 by naive T cells reflects differential dynamic interactions with dendritic cells.

Hurez V, Saparov A, Tousson A, Fuller MJ, Kubo T, Oliver J, Weaver BT, Weaver CT - J. Exp. Med. (2003)

Limited induction of IL-2+ cells is a consistent feature of the primary CD4 T cell response induced by distinct, mature DC populations. DC populations were as follows: splenic DCs purified from BALB/c mice, bone marrow-derived DCs (BM DCs), and a mature hybrid DC line (V-2 DC line). 5 × 105 CD4 T cells from DO11.IL-2P/GFP mice were incubated in culture wells with 1.5 × 105 DCs from each source with or without 10 μg/ml OVAp for 48 h. The frequency of CD4+, GFP+, and CD25+ cells was assessed by flow cytometry on the lymphoid gate.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2196090&req=5

fig1: Limited induction of IL-2+ cells is a consistent feature of the primary CD4 T cell response induced by distinct, mature DC populations. DC populations were as follows: splenic DCs purified from BALB/c mice, bone marrow-derived DCs (BM DCs), and a mature hybrid DC line (V-2 DC line). 5 × 105 CD4 T cells from DO11.IL-2P/GFP mice were incubated in culture wells with 1.5 × 105 DCs from each source with or without 10 μg/ml OVAp for 48 h. The frequency of CD4+, GFP+, and CD25+ cells was assessed by flow cytometry on the lymphoid gate.
Mentions: Distinct populations of mature DCs were surveyed for their capacity to activate a clonal CD4 T cell response using the DO11.IL-2P/GFP transgenic model. Three populations of mature DCs were examined: (a) purified CD11c+ DCs isolated from spleen; (b) BM-derived mature DCs (24); and (c) the V-2 control DC hybrid line (25, 26). Naive CD4 T cells from DO11.IL-2P/GFP mice were incubated with DCs from each source and the frequency of IL-2/GFP+ cells was assessed 20 h after stimulation with or without OVA peptide (Fig. 1). In all cases, the frequency of GFP+ cells was less than one fourth of the CD4 T cell population (spleen DCs, 23.7%; BM DCs, 20.5%; and V-2 DC line, 20.9%). In contrast, 60–80% of CD4 T cells up-regulated CD25 irrespective of the type of DC used (Fig. 1). Thus, expression of IL-2/GFP by a limited subpopulation of antigen-activated naive T cells was a common feature of the clonal response, and was independent of the type of mature DC population used to present antigen.

Bottom Line: T cells destined to produce IL-2 required prolonged interactions with DCs, whereas most T cells established only transient interactions with DCs and were activated, but did not express IL-2.Extended conjugation of T cells with DCs was not always sufficient to initiate IL-2 expression.Thus, there is intrinsic variability in clonal T cell populations that restricts IL-2 commitment, and prolonged engagement with mature DCs is necessary, but not sufficient, for IL-2 gene transcription.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, University of Alabama at Birmingham, AL 35294, USA.

ABSTRACT
Limited frequencies of T cells express IL-2 in primary antigenic responses, despite activation marker expression and proliferation by most clonal members. To define the basis for restricted IL-2 expression, a videomicroscopic system and IL-2 reporter transgenic model were used to characterize dendritic cell (DC)-T cell interactions. T cells destined to produce IL-2 required prolonged interactions with DCs, whereas most T cells established only transient interactions with DCs and were activated, but did not express IL-2. Extended conjugation of T cells with DCs was not always sufficient to initiate IL-2 expression. Thus, there is intrinsic variability in clonal T cell populations that restricts IL-2 commitment, and prolonged engagement with mature DCs is necessary, but not sufficient, for IL-2 gene transcription.

Show MeSH