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TRANCE (tumor necrosis factor [TNF]-related activation-induced cytokine), a new TNF family member predominantly expressed in T cells, is a dendritic cell-specific survival factor.

Wong BR, Josien R, Lee SY, Sauter B, Li HL, Steinman RM, Choi Y - J. Exp. Med. (1997)

Bottom Line: Here, we show that high levels of TRANCE-R are detected on mature dendritic cells (DCs) but not on freshly isolated B cells, T cells, or macrophages.The resulting increase in DC survival is accompanied by a proportional increase in DC-mediated T cell proliferation in a mixed leukocyte reaction.TRANCE does not induce the proliferation of or increase the survival of T or B cells.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Immunology, The Rockefeller University, New York 10021, USA.

ABSTRACT
TRANCE (tumor necrosis factor [TNF]-related activation-induced cytokine) is a new member of the TNF family that is induced upon T cell receptor engagement and activates c-Jun N-terminal kinase (JNK) after interaction with its putative receptor (TRANCE-R). In addition, TRANCE expression is restricted to lymphoid organs and T cells. Here, we show that high levels of TRANCE-R are detected on mature dendritic cells (DCs) but not on freshly isolated B cells, T cells, or macrophages. Signaling by TRANCE-R appears to be dependent on TNF receptor-associated factor 2 (TRAF2), since JNK induction is impaired in cells from transgenic mice overexpressing a dominant negative TRAF2 protein. TRANCE inhibits apoptosis of mouse bone marrow-derived DCs and human monocyte-derived DCs in vitro. The resulting increase in DC survival is accompanied by a proportional increase in DC-mediated T cell proliferation in a mixed leukocyte reaction. TRANCE upregulates Bcl-xL expression, suggesting a potential mechanism for enhanced DC survival. TRANCE does not induce the proliferation of or increase the survival of T or B cells. Therefore, TRANCE is a new DC-restricted survival factor that mediates T cell-DC communication and may provide a tool to selectively enhance DC activity.

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Cell surface marker expression and T cell stimulatory function of TRANCE-treated BMDCs. (A) 2.5 × 103 BMDCs were cultured  with increasing doses of TRANCE in a final volume of 100 μl in triplicate in flat-bottomed 96-well plates. After 48 h, 105 purified allogeneic T  cells in 100 μl were added in each well and [3H]thymidine incorporation  was assessed after 3 d of culture. One experiment out of three is shown.  (B) 2.5 × 104 BMDCs were cultured in the presence or absence of  TRANCE or CD40L for 48 h. After washing and counting the cells, dilutions of live cells were cultured with 105 purified allogeneic T cells and  [3H]thymidine incorporation was assessed after 3 d of culture. (C) BMDCs  were cultured in complete medium for 24 h in the presence (solid lines) or  absence (dotted lines) of soluble FLAG-TRANCE (1 μg/ml) and analyzed  for the indicated surface markers expression by FACS® after gating the  live cells. Similar results were obtained after 48 h of culture.
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Figure 3: Cell surface marker expression and T cell stimulatory function of TRANCE-treated BMDCs. (A) 2.5 × 103 BMDCs were cultured with increasing doses of TRANCE in a final volume of 100 μl in triplicate in flat-bottomed 96-well plates. After 48 h, 105 purified allogeneic T cells in 100 μl were added in each well and [3H]thymidine incorporation was assessed after 3 d of culture. One experiment out of three is shown. (B) 2.5 × 104 BMDCs were cultured in the presence or absence of TRANCE or CD40L for 48 h. After washing and counting the cells, dilutions of live cells were cultured with 105 purified allogeneic T cells and [3H]thymidine incorporation was assessed after 3 d of culture. (C) BMDCs were cultured in complete medium for 24 h in the presence (solid lines) or absence (dotted lines) of soluble FLAG-TRANCE (1 μg/ml) and analyzed for the indicated surface markers expression by FACS® after gating the live cells. Similar results were obtained after 48 h of culture.

Mentions: To examine the functional consequences of TRANCE on DCs we measured the MLR-stimulating ability of DCs treated with TRANCE. Increasing doses of FLAG-TRANCE enhanced DC survival at 48 h, which in turn led to a proportional increase in the stimulation of T cell proliferation (Fig. 3 A). When equivalent numbers of viable TRANCE-treated or untreated DCs were used in an MLR, there were no differences in T cell proliferation, suggesting that changes in the expression of costimulatory and antigen-presenting molecules did not account for the enhanced T cell proliferation (Fig. 3 B). To verify this, the levels of several surface markers were tested by FACS® to evaluate any TRANCE-mediated changes to the DC phenotype. There was a slight but reproducible downregulation of MHC class II expression and a slight upregulation of MHC class I expression (Fig. 3 C). There were no TRANCE-mediated perturbations in the expression of the costimulatory molecules CD80 (B7-1) or CD86 (B7-2), and no changes in the expression of the adhesion molecules intracellular adhesion molecule (ICAM)–1, CD11b, and CD11c. Interestingly, CD40 expression increased but Fas and TRANCE-R did not. In sum, TRANCE enhances DC-mediated T cell proliferation by increasing the survival of DCs.


TRANCE (tumor necrosis factor [TNF]-related activation-induced cytokine), a new TNF family member predominantly expressed in T cells, is a dendritic cell-specific survival factor.

Wong BR, Josien R, Lee SY, Sauter B, Li HL, Steinman RM, Choi Y - J. Exp. Med. (1997)

Cell surface marker expression and T cell stimulatory function of TRANCE-treated BMDCs. (A) 2.5 × 103 BMDCs were cultured  with increasing doses of TRANCE in a final volume of 100 μl in triplicate in flat-bottomed 96-well plates. After 48 h, 105 purified allogeneic T  cells in 100 μl were added in each well and [3H]thymidine incorporation  was assessed after 3 d of culture. One experiment out of three is shown.  (B) 2.5 × 104 BMDCs were cultured in the presence or absence of  TRANCE or CD40L for 48 h. After washing and counting the cells, dilutions of live cells were cultured with 105 purified allogeneic T cells and  [3H]thymidine incorporation was assessed after 3 d of culture. (C) BMDCs  were cultured in complete medium for 24 h in the presence (solid lines) or  absence (dotted lines) of soluble FLAG-TRANCE (1 μg/ml) and analyzed  for the indicated surface markers expression by FACS® after gating the  live cells. Similar results were obtained after 48 h of culture.
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Related In: Results  -  Collection

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Figure 3: Cell surface marker expression and T cell stimulatory function of TRANCE-treated BMDCs. (A) 2.5 × 103 BMDCs were cultured with increasing doses of TRANCE in a final volume of 100 μl in triplicate in flat-bottomed 96-well plates. After 48 h, 105 purified allogeneic T cells in 100 μl were added in each well and [3H]thymidine incorporation was assessed after 3 d of culture. One experiment out of three is shown. (B) 2.5 × 104 BMDCs were cultured in the presence or absence of TRANCE or CD40L for 48 h. After washing and counting the cells, dilutions of live cells were cultured with 105 purified allogeneic T cells and [3H]thymidine incorporation was assessed after 3 d of culture. (C) BMDCs were cultured in complete medium for 24 h in the presence (solid lines) or absence (dotted lines) of soluble FLAG-TRANCE (1 μg/ml) and analyzed for the indicated surface markers expression by FACS® after gating the live cells. Similar results were obtained after 48 h of culture.
Mentions: To examine the functional consequences of TRANCE on DCs we measured the MLR-stimulating ability of DCs treated with TRANCE. Increasing doses of FLAG-TRANCE enhanced DC survival at 48 h, which in turn led to a proportional increase in the stimulation of T cell proliferation (Fig. 3 A). When equivalent numbers of viable TRANCE-treated or untreated DCs were used in an MLR, there were no differences in T cell proliferation, suggesting that changes in the expression of costimulatory and antigen-presenting molecules did not account for the enhanced T cell proliferation (Fig. 3 B). To verify this, the levels of several surface markers were tested by FACS® to evaluate any TRANCE-mediated changes to the DC phenotype. There was a slight but reproducible downregulation of MHC class II expression and a slight upregulation of MHC class I expression (Fig. 3 C). There were no TRANCE-mediated perturbations in the expression of the costimulatory molecules CD80 (B7-1) or CD86 (B7-2), and no changes in the expression of the adhesion molecules intracellular adhesion molecule (ICAM)–1, CD11b, and CD11c. Interestingly, CD40 expression increased but Fas and TRANCE-R did not. In sum, TRANCE enhances DC-mediated T cell proliferation by increasing the survival of DCs.

Bottom Line: Here, we show that high levels of TRANCE-R are detected on mature dendritic cells (DCs) but not on freshly isolated B cells, T cells, or macrophages.The resulting increase in DC survival is accompanied by a proportional increase in DC-mediated T cell proliferation in a mixed leukocyte reaction.TRANCE does not induce the proliferation of or increase the survival of T or B cells.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Immunology, The Rockefeller University, New York 10021, USA.

ABSTRACT
TRANCE (tumor necrosis factor [TNF]-related activation-induced cytokine) is a new member of the TNF family that is induced upon T cell receptor engagement and activates c-Jun N-terminal kinase (JNK) after interaction with its putative receptor (TRANCE-R). In addition, TRANCE expression is restricted to lymphoid organs and T cells. Here, we show that high levels of TRANCE-R are detected on mature dendritic cells (DCs) but not on freshly isolated B cells, T cells, or macrophages. Signaling by TRANCE-R appears to be dependent on TNF receptor-associated factor 2 (TRAF2), since JNK induction is impaired in cells from transgenic mice overexpressing a dominant negative TRAF2 protein. TRANCE inhibits apoptosis of mouse bone marrow-derived DCs and human monocyte-derived DCs in vitro. The resulting increase in DC survival is accompanied by a proportional increase in DC-mediated T cell proliferation in a mixed leukocyte reaction. TRANCE upregulates Bcl-xL expression, suggesting a potential mechanism for enhanced DC survival. TRANCE does not induce the proliferation of or increase the survival of T or B cells. Therefore, TRANCE is a new DC-restricted survival factor that mediates T cell-DC communication and may provide a tool to selectively enhance DC activity.

Show MeSH
Related in: MedlinePlus