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4-1BB ligand, a member of the TNF family, is important for the generation of antiviral CD8 T cell responses.
J Immunol. 1999 Nov 01; 163(9):4859-68.JI

Abstract

4-1BB (CD137) is a costimulatory molecule expressed on activated T cells and interacts with 4-1BB ligand (4-1BBL) on APCs. To investigate the role of 4-1BB costimulation for the development of primary immune responses, 4-1BBL-deficient (4-1BBL-/-) mice were infected with lymphocytic choriomeningitis virus (LCMV). 4-1BBL-/- mice were able to generate CTL and eliminate acute LCMV infection with normal kinetics, but CD8 T cell expansion was 2- to 3-fold lower than in wild-type (+/+) mice. In the same mice, virus-specific CD4 Th and B cell responses were minimally affected, indicating that 4-1BB costimulation preferentially affects CD8 T cell responses. This result contrasts with our earlier work with CD40L-deficient (CD40L-/-) mice, in which the CD8 T cell response was unaffected and the CD4 T cell response was markedly impaired. When both 4-1BBL- and B7-dependent signals were absent, CD8 T cell expansion was further reduced, resulting in lower CTL activity and impairing their ability to clear LCMV. Altogether, these results indicate that T cells have distinct costimulatory requirements: optimal CD8 responses require 4-1BBL-dependent interactions, whereas CD4 responses are minimally affected by 4-1BB costimulation, but require CD40-CD40L and B7-dependent interactions.

Authors+Show Affiliations

The Carlos and Marguerite Mason Transplantation Biology Research Center, Department of Surgery, Emory University School of Medicine, Atlanta, GA 30322, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

10528187

Citation

Tan, J T., et al. "4-1BB Ligand, a Member of the TNF Family, Is Important for the Generation of Antiviral CD8 T Cell Responses." Journal of Immunology (Baltimore, Md. : 1950), vol. 163, no. 9, 1999, pp. 4859-68.
Tan JT, Whitmire JK, Ahmed R, et al. 4-1BB ligand, a member of the TNF family, is important for the generation of antiviral CD8 T cell responses. J Immunol. 1999;163(9):4859-68.
Tan, J. T., Whitmire, J. K., Ahmed, R., Pearson, T. C., & Larsen, C. P. (1999). 4-1BB ligand, a member of the TNF family, is important for the generation of antiviral CD8 T cell responses. Journal of Immunology (Baltimore, Md. : 1950), 163(9), 4859-68.
Tan JT, et al. 4-1BB Ligand, a Member of the TNF Family, Is Important for the Generation of Antiviral CD8 T Cell Responses. J Immunol. 1999 Nov 1;163(9):4859-68. PubMed PMID: 10528187.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 4-1BB ligand, a member of the TNF family, is important for the generation of antiviral CD8 T cell responses. AU - Tan,J T, AU - Whitmire,J K, AU - Ahmed,R, AU - Pearson,T C, AU - Larsen,C P, PY - 1999/10/21/pubmed PY - 1999/10/21/medline PY - 1999/10/21/entrez SP - 4859 EP - 68 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J. Immunol. VL - 163 IS - 9 N2 - 4-1BB (CD137) is a costimulatory molecule expressed on activated T cells and interacts with 4-1BB ligand (4-1BBL) on APCs. To investigate the role of 4-1BB costimulation for the development of primary immune responses, 4-1BBL-deficient (4-1BBL-/-) mice were infected with lymphocytic choriomeningitis virus (LCMV). 4-1BBL-/- mice were able to generate CTL and eliminate acute LCMV infection with normal kinetics, but CD8 T cell expansion was 2- to 3-fold lower than in wild-type (+/+) mice. In the same mice, virus-specific CD4 Th and B cell responses were minimally affected, indicating that 4-1BB costimulation preferentially affects CD8 T cell responses. This result contrasts with our earlier work with CD40L-deficient (CD40L-/-) mice, in which the CD8 T cell response was unaffected and the CD4 T cell response was markedly impaired. When both 4-1BBL- and B7-dependent signals were absent, CD8 T cell expansion was further reduced, resulting in lower CTL activity and impairing their ability to clear LCMV. Altogether, these results indicate that T cells have distinct costimulatory requirements: optimal CD8 responses require 4-1BBL-dependent interactions, whereas CD4 responses are minimally affected by 4-1BB costimulation, but require CD40-CD40L and B7-dependent interactions. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/10528187/4_1BB_ligand_a_member_of_the_TNF_family_is_important_for_the_generation_of_antiviral_CD8_T_cell_responses_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=10528187 DB - PRIME DP - Unbound Medicine ER -