Limits...
Membrane tumor necrosis factor (TNF) induced cooperative signaling of TNFR60 and TNFR80 favors induction of cell death rather than virus production in HIV-infected T cells.

Lazdins JK, Grell M, Walker MR, Woods-Cook K, Scheurich P, Pfizenmaier K - J. Exp. Med. (1997)

Bottom Line: In the present study we have demonstrated by means of antagonistic and agonistic receptor-specific antibodies that in latently infected lymphocytic (ACH-2) cells the TNFR60 plays a dominant role in signaling HIV production, although selective activation of TNFR80 by receptor-specific antibodies can also induce HIV production.Unexpectedly, when both TNFRs were activated simultaneously by agonistic antibodies or coculture with cells expressing a noncleavable membrane form of TNF, HIV production was downregulated and induction of cell death was enhanced in ACH-2 cells.These data provide evidence for the differential trigger potential of membrane versus soluble TNF and show that TNFR80 is an important modulator of TNF responsiveness of HIV-infected T cells via cooperative signaling with TNFR60.

View Article: PubMed Central - PubMed

Affiliation: Division Pharma, Ciba, Basel, Switzerland.

ABSTRACT
Tumor necrosis factor (TNF) and lymphotoxin (LT) are highly pleiotropic cytokines that play a central role in regulating HIV-1 replication. These cytokines express their activities through two membrane receptors, TNFR60 (p55-60) and TNFR80 (p75-80). In the present study we have demonstrated by means of antagonistic and agonistic receptor-specific antibodies that in latently infected lymphocytic (ACH-2) cells the TNFR60 plays a dominant role in signaling HIV production, although selective activation of TNFR80 by receptor-specific antibodies can also induce HIV production. Unexpectedly, when both TNFRs were activated simultaneously by agonistic antibodies or coculture with cells expressing a noncleavable membrane form of TNF, HIV production was downregulated and induction of cell death was enhanced in ACH-2 cells. More relevant, in vitro HIV-infected peripheral blood lymphocytes cocultured with cells expressing membrane TNF underwent rapid induction of apoptosis with a subsequent reduced HIV production of these lymphocytes cultures. This was not observed with HIV-infected lymphocytes treated with soluble TNF. These data provide evidence for the differential trigger potential of membrane versus soluble TNF and show that TNFR80 is an important modulator of TNF responsiveness of HIV-infected T cells via cooperative signaling with TNFR60.

Show MeSH

Related in: MedlinePlus

Coexpression of TNFR60 and TNFR80 in ACH-2 cells.  TNFR expression was determined by indirect immunofluorescence flow  cytometry analyses using TNFR60-specific monoclonal (H398) and  TNFR80-specific polyclonal antibodies (M80) and FITC-conjugated secondary reagents as described in Materials and Methods. The open histogram represents staining by control antibody, fluorescence intensity obtained by staining with receptor-specific antibodies is shown in black.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2196100&req=5

Figure 1: Coexpression of TNFR60 and TNFR80 in ACH-2 cells. TNFR expression was determined by indirect immunofluorescence flow cytometry analyses using TNFR60-specific monoclonal (H398) and TNFR80-specific polyclonal antibodies (M80) and FITC-conjugated secondary reagents as described in Materials and Methods. The open histogram represents staining by control antibody, fluorescence intensity obtained by staining with receptor-specific antibodies is shown in black.

Mentions: To assess the role of the two TNFRs in TNF-mediated activation of HIV production in ACH-2 cells, membrane expression of both TNFR60 and TNFR80 was verified by immunofluorescence flow cytometry (Fig. 1). In contrast, the non HIVinfected parental cell line CEM only expressed TNFR60, suggesting an induction of TNFR80 in ACH-2 cells during establishment of latent HIV infection.


Membrane tumor necrosis factor (TNF) induced cooperative signaling of TNFR60 and TNFR80 favors induction of cell death rather than virus production in HIV-infected T cells.

Lazdins JK, Grell M, Walker MR, Woods-Cook K, Scheurich P, Pfizenmaier K - J. Exp. Med. (1997)

Coexpression of TNFR60 and TNFR80 in ACH-2 cells.  TNFR expression was determined by indirect immunofluorescence flow  cytometry analyses using TNFR60-specific monoclonal (H398) and  TNFR80-specific polyclonal antibodies (M80) and FITC-conjugated secondary reagents as described in Materials and Methods. The open histogram represents staining by control antibody, fluorescence intensity obtained by staining with receptor-specific antibodies is shown in black.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2196100&req=5

Figure 1: Coexpression of TNFR60 and TNFR80 in ACH-2 cells. TNFR expression was determined by indirect immunofluorescence flow cytometry analyses using TNFR60-specific monoclonal (H398) and TNFR80-specific polyclonal antibodies (M80) and FITC-conjugated secondary reagents as described in Materials and Methods. The open histogram represents staining by control antibody, fluorescence intensity obtained by staining with receptor-specific antibodies is shown in black.
Mentions: To assess the role of the two TNFRs in TNF-mediated activation of HIV production in ACH-2 cells, membrane expression of both TNFR60 and TNFR80 was verified by immunofluorescence flow cytometry (Fig. 1). In contrast, the non HIVinfected parental cell line CEM only expressed TNFR60, suggesting an induction of TNFR80 in ACH-2 cells during establishment of latent HIV infection.

Bottom Line: In the present study we have demonstrated by means of antagonistic and agonistic receptor-specific antibodies that in latently infected lymphocytic (ACH-2) cells the TNFR60 plays a dominant role in signaling HIV production, although selective activation of TNFR80 by receptor-specific antibodies can also induce HIV production.Unexpectedly, when both TNFRs were activated simultaneously by agonistic antibodies or coculture with cells expressing a noncleavable membrane form of TNF, HIV production was downregulated and induction of cell death was enhanced in ACH-2 cells.These data provide evidence for the differential trigger potential of membrane versus soluble TNF and show that TNFR80 is an important modulator of TNF responsiveness of HIV-infected T cells via cooperative signaling with TNFR60.

View Article: PubMed Central - PubMed

Affiliation: Division Pharma, Ciba, Basel, Switzerland.

ABSTRACT
Tumor necrosis factor (TNF) and lymphotoxin (LT) are highly pleiotropic cytokines that play a central role in regulating HIV-1 replication. These cytokines express their activities through two membrane receptors, TNFR60 (p55-60) and TNFR80 (p75-80). In the present study we have demonstrated by means of antagonistic and agonistic receptor-specific antibodies that in latently infected lymphocytic (ACH-2) cells the TNFR60 plays a dominant role in signaling HIV production, although selective activation of TNFR80 by receptor-specific antibodies can also induce HIV production. Unexpectedly, when both TNFRs were activated simultaneously by agonistic antibodies or coculture with cells expressing a noncleavable membrane form of TNF, HIV production was downregulated and induction of cell death was enhanced in ACH-2 cells. More relevant, in vitro HIV-infected peripheral blood lymphocytes cocultured with cells expressing membrane TNF underwent rapid induction of apoptosis with a subsequent reduced HIV production of these lymphocytes cultures. This was not observed with HIV-infected lymphocytes treated with soluble TNF. These data provide evidence for the differential trigger potential of membrane versus soluble TNF and show that TNFR80 is an important modulator of TNF responsiveness of HIV-infected T cells via cooperative signaling with TNFR60.

Show MeSH
Related in: MedlinePlus