Limits...
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.

Show MeSH

Related in: MedlinePlus

TRANCE is a DC survival factor that upregulates Bcl-xL.  (A) BMDCs were cultured in complete medium in the presence or absence of recombinant TRANCE (1 μg/ml) for 48 h and were then visualized under an inverted light microscope. (B) Duplicate wells containing  3 × 104 BMDCs were cultured with increasing doses of recombinant  TRANCE in complete medium in flat-bottomed 96-well plates. The  percentage of cell survival was assessed 48 h later by trypan blue exclusion.  The average of three experiments, and the SEMs, are shown. (C) 3 × 104  BMDCs were cultured in complete medium in the presence or absence of  recombinant TRANCE (1 μg/ml) or mCD8-CD40L (1/1,000 of the  culture supernatants). Cell viablity was assessed daily by trypan blue exclusion. Representative data of three independent experiments are shown.  (D) 3 × 104 GM-CSFs and IL-4 stimulated human monocyte-derived  DCs were cultured for 2 d in monocyte conditioned medium to generate  mature DCs (26). Thereafter, DCs were cultured in the presence or absence of recombinant TRANCE (1 μg/ml) and cell viability was assessed  each day by trypan blue exclusion. (E) 50 μg of protein extracted from  BMDCs that had been cultured for 24 h as described in Fig. 2 C were analyzed for Bcl-2 and Bcl-xL protein expression by Western blot analysis.  Basal levels of Bcl-2 and Bcl-xL were determined in day 8 BMDCs (0 h).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2199171&req=5

Figure 2: TRANCE is a DC survival factor that upregulates Bcl-xL. (A) BMDCs were cultured in complete medium in the presence or absence of recombinant TRANCE (1 μg/ml) for 48 h and were then visualized under an inverted light microscope. (B) Duplicate wells containing 3 × 104 BMDCs were cultured with increasing doses of recombinant TRANCE in complete medium in flat-bottomed 96-well plates. The percentage of cell survival was assessed 48 h later by trypan blue exclusion. The average of three experiments, and the SEMs, are shown. (C) 3 × 104 BMDCs were cultured in complete medium in the presence or absence of recombinant TRANCE (1 μg/ml) or mCD8-CD40L (1/1,000 of the culture supernatants). Cell viablity was assessed daily by trypan blue exclusion. Representative data of three independent experiments are shown. (D) 3 × 104 GM-CSFs and IL-4 stimulated human monocyte-derived DCs were cultured for 2 d in monocyte conditioned medium to generate mature DCs (26). Thereafter, DCs were cultured in the presence or absence of recombinant TRANCE (1 μg/ml) and cell viability was assessed each day by trypan blue exclusion. (E) 50 μg of protein extracted from BMDCs that had been cultured for 24 h as described in Fig. 2 C were analyzed for Bcl-2 and Bcl-xL protein expression by Western blot analysis. Basal levels of Bcl-2 and Bcl-xL were determined in day 8 BMDCs (0 h).

Mentions: The biological effects of TRANCE were further studied on mature DCs. TRANCE-treated DCs formed densely packed clusters whereas control, untreated cells exhibited relatively sparse aggregates (Fig. 2 A). In addition, mature BMDCs treated with FLAG-TRANCE were significantly protected from spontaneous cell death compared to untreated cells. This effect was dependent on the dose of TRANCE (Fig. 2 B). hCD8-TRANCE elicited similar results (data not shown). This effect was not due to increased cell proliferation since the total number of cells remained the same over time (data not shown). TRANCE significantly prevented DC cell death until day 6, whereas untreated cells were almost completely dead by day 3 (Fig. 2 C). A similar effect on DC survival was observed with human monocyte-derived DC (Fig. 2 D). Confirming previous data, CD40L also induced the clustering of DCs (data not shown; 28, 29) and enhanced DC survival comparably to TRANCE (Fig. 2 C).


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)

TRANCE is a DC survival factor that upregulates Bcl-xL.  (A) BMDCs were cultured in complete medium in the presence or absence of recombinant TRANCE (1 μg/ml) for 48 h and were then visualized under an inverted light microscope. (B) Duplicate wells containing  3 × 104 BMDCs were cultured with increasing doses of recombinant  TRANCE in complete medium in flat-bottomed 96-well plates. The  percentage of cell survival was assessed 48 h later by trypan blue exclusion.  The average of three experiments, and the SEMs, are shown. (C) 3 × 104  BMDCs were cultured in complete medium in the presence or absence of  recombinant TRANCE (1 μg/ml) or mCD8-CD40L (1/1,000 of the  culture supernatants). Cell viablity was assessed daily by trypan blue exclusion. Representative data of three independent experiments are shown.  (D) 3 × 104 GM-CSFs and IL-4 stimulated human monocyte-derived  DCs were cultured for 2 d in monocyte conditioned medium to generate  mature DCs (26). Thereafter, DCs were cultured in the presence or absence of recombinant TRANCE (1 μg/ml) and cell viability was assessed  each day by trypan blue exclusion. (E) 50 μg of protein extracted from  BMDCs that had been cultured for 24 h as described in Fig. 2 C were analyzed for Bcl-2 and Bcl-xL protein expression by Western blot analysis.  Basal levels of Bcl-2 and Bcl-xL were determined in day 8 BMDCs (0 h).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2199171&req=5

Figure 2: TRANCE is a DC survival factor that upregulates Bcl-xL. (A) BMDCs were cultured in complete medium in the presence or absence of recombinant TRANCE (1 μg/ml) for 48 h and were then visualized under an inverted light microscope. (B) Duplicate wells containing 3 × 104 BMDCs were cultured with increasing doses of recombinant TRANCE in complete medium in flat-bottomed 96-well plates. The percentage of cell survival was assessed 48 h later by trypan blue exclusion. The average of three experiments, and the SEMs, are shown. (C) 3 × 104 BMDCs were cultured in complete medium in the presence or absence of recombinant TRANCE (1 μg/ml) or mCD8-CD40L (1/1,000 of the culture supernatants). Cell viablity was assessed daily by trypan blue exclusion. Representative data of three independent experiments are shown. (D) 3 × 104 GM-CSFs and IL-4 stimulated human monocyte-derived DCs were cultured for 2 d in monocyte conditioned medium to generate mature DCs (26). Thereafter, DCs were cultured in the presence or absence of recombinant TRANCE (1 μg/ml) and cell viability was assessed each day by trypan blue exclusion. (E) 50 μg of protein extracted from BMDCs that had been cultured for 24 h as described in Fig. 2 C were analyzed for Bcl-2 and Bcl-xL protein expression by Western blot analysis. Basal levels of Bcl-2 and Bcl-xL were determined in day 8 BMDCs (0 h).
Mentions: The biological effects of TRANCE were further studied on mature DCs. TRANCE-treated DCs formed densely packed clusters whereas control, untreated cells exhibited relatively sparse aggregates (Fig. 2 A). In addition, mature BMDCs treated with FLAG-TRANCE were significantly protected from spontaneous cell death compared to untreated cells. This effect was dependent on the dose of TRANCE (Fig. 2 B). hCD8-TRANCE elicited similar results (data not shown). This effect was not due to increased cell proliferation since the total number of cells remained the same over time (data not shown). TRANCE significantly prevented DC cell death until day 6, whereas untreated cells were almost completely dead by day 3 (Fig. 2 C). A similar effect on DC survival was observed with human monocyte-derived DC (Fig. 2 D). Confirming previous data, CD40L also induced the clustering of DCs (data not shown; 28, 29) and enhanced DC survival comparably to TRANCE (Fig. 2 C).

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