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Analysis of 4-1BB ligand (4-1BBL)-deficient mice and of mice lacking both 4-1BBL and CD28 reveals a role for 4-1BBL in skin allograft rejection and in the cytotoxic T cell response to influenza virus.
J Immunol. 1999 Nov 01; 163(9):4833-41.JI

Abstract

4-1BB ligand (4-1BBL) is a member of the TNF family expressed on activated APC. 4-1BBL binds to 4-1BB (CD137) on activated CD4 and CD8 T cells and in conjunction with strong signals through the TCR provides a CD28-independent costimulatory signal leading to high level IL-2 production by primary resting T cells. Here we report the immunological characterization of mice lacking 4-1BBL and of mice lacking both 4-1BBL and CD28. 4-1BBL-/- mice mount neutralizing IgM and IgG responses to vesicular stomatitis virus that are indistinguishable from those of wild-type mice. 4-1BBL-/- mice show unimpaired CTL responses to lymphocytic choriomeningitis virus (LCMV) and exhibit normal skin allograft rejection but have a weaker CTL response to influenza virus than wild-type mice. 4-1BBL-/-CD28-/- mice retain the CTL response to LCMV, respond poorly to influenza virus, and exhibit a delay in skin allograft rejection. In agreement with these in vivo results, allogeneic CTL responses of CD28-/- but not CD28+/+ T cells to 4-1BBL-expressing APC are substantially inhibited by soluble 4-1BB receptor as is the in vitro secondary response of CD28+ T cells to influenza virus peptides. TCR-transgenic CD28-/- LCMV glycoprotein-specific T cells are insensitive to the presence of 4-1BBL when a wild-type peptide is used, but the response to a weak agonist peptide is greatly augmented by the presence of 4-1BBL. These results further substantiate the idea that different immune responses vary in their dependence on costimulation and suggest a role for 4-1BBL in augmenting suboptimal CTL responses in vivo.

Authors+Show Affiliations

Department of Immunology, University of Toronto, Ontario, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10528184

Citation

DeBenedette, M A., et al. "Analysis of 4-1BB Ligand (4-1BBL)-deficient Mice and of Mice Lacking Both 4-1BBL and CD28 Reveals a Role for 4-1BBL in Skin Allograft Rejection and in the Cytotoxic T Cell Response to Influenza Virus." Journal of Immunology (Baltimore, Md. : 1950), vol. 163, no. 9, 1999, pp. 4833-41.
DeBenedette MA, Wen T, Bachmann MF, et al. Analysis of 4-1BB ligand (4-1BBL)-deficient mice and of mice lacking both 4-1BBL and CD28 reveals a role for 4-1BBL in skin allograft rejection and in the cytotoxic T cell response to influenza virus. J Immunol. 1999;163(9):4833-41.
DeBenedette, M. A., Wen, T., Bachmann, M. F., Ohashi, P. S., Barber, B. H., Stocking, K. L., Peschon, J. J., & Watts, T. H. (1999). Analysis of 4-1BB ligand (4-1BBL)-deficient mice and of mice lacking both 4-1BBL and CD28 reveals a role for 4-1BBL in skin allograft rejection and in the cytotoxic T cell response to influenza virus. Journal of Immunology (Baltimore, Md. : 1950), 163(9), 4833-41.
DeBenedette MA, et al. Analysis of 4-1BB Ligand (4-1BBL)-deficient Mice and of Mice Lacking Both 4-1BBL and CD28 Reveals a Role for 4-1BBL in Skin Allograft Rejection and in the Cytotoxic T Cell Response to Influenza Virus. J Immunol. 1999 Nov 1;163(9):4833-41. PubMed PMID: 10528184.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Analysis of 4-1BB ligand (4-1BBL)-deficient mice and of mice lacking both 4-1BBL and CD28 reveals a role for 4-1BBL in skin allograft rejection and in the cytotoxic T cell response to influenza virus. AU - DeBenedette,M A, AU - Wen,T, AU - Bachmann,M F, AU - Ohashi,P S, AU - Barber,B H, AU - Stocking,K L, AU - Peschon,J J, AU - Watts,T H, PY - 1999/10/21/pubmed PY - 1999/10/21/medline PY - 1999/10/21/entrez SP - 4833 EP - 41 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J. Immunol. VL - 163 IS - 9 N2 - 4-1BB ligand (4-1BBL) is a member of the TNF family expressed on activated APC. 4-1BBL binds to 4-1BB (CD137) on activated CD4 and CD8 T cells and in conjunction with strong signals through the TCR provides a CD28-independent costimulatory signal leading to high level IL-2 production by primary resting T cells. Here we report the immunological characterization of mice lacking 4-1BBL and of mice lacking both 4-1BBL and CD28. 4-1BBL-/- mice mount neutralizing IgM and IgG responses to vesicular stomatitis virus that are indistinguishable from those of wild-type mice. 4-1BBL-/- mice show unimpaired CTL responses to lymphocytic choriomeningitis virus (LCMV) and exhibit normal skin allograft rejection but have a weaker CTL response to influenza virus than wild-type mice. 4-1BBL-/-CD28-/- mice retain the CTL response to LCMV, respond poorly to influenza virus, and exhibit a delay in skin allograft rejection. In agreement with these in vivo results, allogeneic CTL responses of CD28-/- but not CD28+/+ T cells to 4-1BBL-expressing APC are substantially inhibited by soluble 4-1BB receptor as is the in vitro secondary response of CD28+ T cells to influenza virus peptides. TCR-transgenic CD28-/- LCMV glycoprotein-specific T cells are insensitive to the presence of 4-1BBL when a wild-type peptide is used, but the response to a weak agonist peptide is greatly augmented by the presence of 4-1BBL. These results further substantiate the idea that different immune responses vary in their dependence on costimulation and suggest a role for 4-1BBL in augmenting suboptimal CTL responses in vivo. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/10528184/Analysis_of_4_1BB_ligand__4_1BBL__deficient_mice_and_of_mice_lacking_both_4_1BBL_and_CD28_reveals_a_role_for_4_1BBL_in_skin_allograft_rejection_and_in_the_cytotoxic_T_cell_response_to_influenza_virus_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=10528184 DB - PRIME DP - Unbound Medicine ER -