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Cooperation between 4-1BB and ICOS in the immune response to influenza virus revealed by studies of CD28/ICOS-deficient mice.
J Immunol. 2005 Dec 01; 175(11):7288-96.JI

Abstract

CD28, ICOS, and 4-1BB each play distinct roles in the CD8 T cell response to influenza virus. CD28-/- mice are severely impaired in primary CD8 T cell expansion and fail to mount a secondary response to influenza. Influenza-specific CD8 T cells expand normally in ICOS-/- mice, with only a small and transient defect late in the primary response and an unimpaired secondary response. Conversely, 4-1BB/4-1BBL interaction is dispensable for the primary CD8 T cell response to influenza, but maintains CD8 T cell survival and controls the size of the secondary response. Previous results showed that a single dose of agonistic anti-4-1BB Ab at priming allowed partial restoration of primary CD8 T cell expansion and full recovery of the secondary CD8 T cell responses to influenza in CD28-/- mice. In this study we show that anti-4-1BB fails to correct the CD8 T cell defect in CD28-/-ICOS-/- mice, suggesting that ICOS partially compensates for CD28 in this model. In support of this hypothesis, we found that anti-4-1BB enhances ICOS expression on both T cell subsets and that anti-4-1BB and anti-ICOS can synergistically activate CD4 and CD8 T cells. Furthermore, ICOS and 4-1BB can cooperate to directly stimulate isolated CD28-/- CD8 T cells. These results reveal a novel interaction between the ICOS and 4-1BB costimulatory pathways as well as unexpected redundancy between CD28 and ICOS in primary CD8 T cell expansion. These findings have implications for costimulation of human T cell responses in diseases such as AIDS or rheumatoid arthritis, in which CD28- T cells accumulate.

Authors+Show Affiliations

Department of Immunology, University of Toronto, Ontario, Canada.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

Language

eng

PubMed ID

16301634

Citation

Vidric, Mariana, et al. "Cooperation Between 4-1BB and ICOS in the Immune Response to Influenza Virus Revealed By Studies of CD28/ICOS-deficient Mice." Journal of Immunology (Baltimore, Md. : 1950), vol. 175, no. 11, 2005, pp. 7288-96.
Vidric M, Suh WK, Dianzani U, et al. Cooperation between 4-1BB and ICOS in the immune response to influenza virus revealed by studies of CD28/ICOS-deficient mice. J Immunol. 2005;175(11):7288-96.
Vidric, M., Suh, W. K., Dianzani, U., Mak, T. W., & Watts, T. H. (2005). Cooperation between 4-1BB and ICOS in the immune response to influenza virus revealed by studies of CD28/ICOS-deficient mice. Journal of Immunology (Baltimore, Md. : 1950), 175(11), 7288-96.
Vidric M, et al. Cooperation Between 4-1BB and ICOS in the Immune Response to Influenza Virus Revealed By Studies of CD28/ICOS-deficient Mice. J Immunol. 2005 Dec 1;175(11):7288-96. PubMed PMID: 16301634.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cooperation between 4-1BB and ICOS in the immune response to influenza virus revealed by studies of CD28/ICOS-deficient mice. AU - Vidric,Mariana, AU - Suh,Woong-Kyung, AU - Dianzani,Umberto, AU - Mak,Tak W, AU - Watts,Tania H, PY - 2005/11/23/pubmed PY - 2006/1/18/medline PY - 2005/11/23/entrez SP - 7288 EP - 96 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J. Immunol. VL - 175 IS - 11 N2 - CD28, ICOS, and 4-1BB each play distinct roles in the CD8 T cell response to influenza virus. CD28-/- mice are severely impaired in primary CD8 T cell expansion and fail to mount a secondary response to influenza. Influenza-specific CD8 T cells expand normally in ICOS-/- mice, with only a small and transient defect late in the primary response and an unimpaired secondary response. Conversely, 4-1BB/4-1BBL interaction is dispensable for the primary CD8 T cell response to influenza, but maintains CD8 T cell survival and controls the size of the secondary response. Previous results showed that a single dose of agonistic anti-4-1BB Ab at priming allowed partial restoration of primary CD8 T cell expansion and full recovery of the secondary CD8 T cell responses to influenza in CD28-/- mice. In this study we show that anti-4-1BB fails to correct the CD8 T cell defect in CD28-/-ICOS-/- mice, suggesting that ICOS partially compensates for CD28 in this model. In support of this hypothesis, we found that anti-4-1BB enhances ICOS expression on both T cell subsets and that anti-4-1BB and anti-ICOS can synergistically activate CD4 and CD8 T cells. Furthermore, ICOS and 4-1BB can cooperate to directly stimulate isolated CD28-/- CD8 T cells. These results reveal a novel interaction between the ICOS and 4-1BB costimulatory pathways as well as unexpected redundancy between CD28 and ICOS in primary CD8 T cell expansion. These findings have implications for costimulation of human T cell responses in diseases such as AIDS or rheumatoid arthritis, in which CD28- T cells accumulate. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/16301634/Cooperation_between_4_1BB_and_ICOS_in_the_immune_response_to_influenza_virus_revealed_by_studies_of_CD28/ICOS_deficient_mice_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=16301634 DB - PRIME DP - Unbound Medicine ER -