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4-1BB costimulation is required for protective anti-viral immunity after peptide vaccination.
J Immunol. 2000 Mar 01; 164(5):2320-5.JI

Abstract

Peptide vaccination induces T cell activation and cytotoxic T cell development. In an effort to understand what factors can improve immune responses to peptide vaccination, the role of 4-1BB (CD137) costimulation was examined, since 4-1BB has been shown to promote T cell responses in other systems. 4-1BBL-deficient (-/-) and wild-type (+/+) mice were immunized with a lipidated lymphocytic choriomeningitis virus (LCMV) peptide NP396-404. Analysis of peptide-specific responses early after immunization by CTL assay, intracellular IFN-gamma staining, and IFN-gamma enzyme-linked immunospot assay (ELISPOT) indicated that CD8 T cell responses were reduced 3- to 10-fold in the absence of 4-1BB costimulation. Moreover, when agonistic anti-4-1BB Ab was given, CD8 T cell responses in 4-1BBL-/- mice were augmented to levels similar to those in 4-1BBL+/+ mice. Two months after immunization, 4-1BBL+/+ mice still had epitope-specific cells and were protected against viral challenge, demonstrating that peptide vaccination can induce long-term protection. In fact, 70% of CD8 T cells were specific for the immunizing peptide after viral challenge, demonstrating that strong, epitope-specific CD8 T cell responses are generated after peptide vaccination. In contrast, peptide-immunized 4-1BBL-/- mice had fewer epitope-specific cells and were impaired in their ability to resolve the infection. These results show that immunization with a single LCMV peptide provides long term protection against LCMV infection and point to costimulatory molecules such as 4-1BB as important components for generating protective immunity after vaccination.

Authors+Show Affiliations

The Carlos and Marguerite Mason Transplantation Biology Research Center and Department of Surgery, Emory University School of Medicine, Atlanta, GA 30322, USA.No affiliation info availableNo 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
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10679066

Citation

Tan, J T., et al. "4-1BB Costimulation Is Required for Protective Anti-viral Immunity After Peptide Vaccination." Journal of Immunology (Baltimore, Md. : 1950), vol. 164, no. 5, 2000, pp. 2320-5.
Tan JT, Whitmire JK, Murali-Krishna K, et al. 4-1BB costimulation is required for protective anti-viral immunity after peptide vaccination. J Immunol. 2000;164(5):2320-5.
Tan, J. T., Whitmire, J. K., Murali-Krishna, K., Ahmed, R., Altman, J. D., Mittler, R. S., Sette, A., Pearson, T. C., & Larsen, C. P. (2000). 4-1BB costimulation is required for protective anti-viral immunity after peptide vaccination. Journal of Immunology (Baltimore, Md. : 1950), 164(5), 2320-5.
Tan JT, et al. 4-1BB Costimulation Is Required for Protective Anti-viral Immunity After Peptide Vaccination. J Immunol. 2000 Mar 1;164(5):2320-5. PubMed PMID: 10679066.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 4-1BB costimulation is required for protective anti-viral immunity after peptide vaccination. AU - Tan,J T, AU - Whitmire,J K, AU - Murali-Krishna,K, AU - Ahmed,R, AU - Altman,J D, AU - Mittler,R S, AU - Sette,A, AU - Pearson,T C, AU - Larsen,C P, PY - 2000/2/29/pubmed PY - 2000/3/25/medline PY - 2000/2/29/entrez SP - 2320 EP - 5 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J. Immunol. VL - 164 IS - 5 N2 - Peptide vaccination induces T cell activation and cytotoxic T cell development. In an effort to understand what factors can improve immune responses to peptide vaccination, the role of 4-1BB (CD137) costimulation was examined, since 4-1BB has been shown to promote T cell responses in other systems. 4-1BBL-deficient (-/-) and wild-type (+/+) mice were immunized with a lipidated lymphocytic choriomeningitis virus (LCMV) peptide NP396-404. Analysis of peptide-specific responses early after immunization by CTL assay, intracellular IFN-gamma staining, and IFN-gamma enzyme-linked immunospot assay (ELISPOT) indicated that CD8 T cell responses were reduced 3- to 10-fold in the absence of 4-1BB costimulation. Moreover, when agonistic anti-4-1BB Ab was given, CD8 T cell responses in 4-1BBL-/- mice were augmented to levels similar to those in 4-1BBL+/+ mice. Two months after immunization, 4-1BBL+/+ mice still had epitope-specific cells and were protected against viral challenge, demonstrating that peptide vaccination can induce long-term protection. In fact, 70% of CD8 T cells were specific for the immunizing peptide after viral challenge, demonstrating that strong, epitope-specific CD8 T cell responses are generated after peptide vaccination. In contrast, peptide-immunized 4-1BBL-/- mice had fewer epitope-specific cells and were impaired in their ability to resolve the infection. These results show that immunization with a single LCMV peptide provides long term protection against LCMV infection and point to costimulatory molecules such as 4-1BB as important components for generating protective immunity after vaccination. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/10679066/4_1BB_costimulation_is_required_for_protective_anti_viral_immunity_after_peptide_vaccination_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=10679066 DB - PRIME DP - Unbound Medicine ER -