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In vivo triggering through 4-1BB enables Th-independent priming of CTL in the presence of an intact CD28 costimulatory pathway.
J Immunol. 2002 Apr 15; 168(8):3755-62.JI

Abstract

Triggering of 4-1BB, a member of the TNFR family, through in vivo administration of agonistic anti-4-1BB Ab delivers a powerful costimulatory signal to CTL. We found this signal to effectively replace the need for CD4(+) T cell help in the cross-priming of tumor-specific CTL immunity. Furthermore, 4-1BB Ab can convert an otherwise tolerogenic peptide vaccine into a formulation capable of efficient CTL priming. Initial activation of naive CTL can occur in the absence of 4-1BB costimulation, but this signal permits increased survival of Ag-stimulated CTL. Because naive CTL do not express 4-1BB at their surface, susceptibility to 4-1BB triggering depends on prior up-regulation of this receptor. We show that this requires both stimulation of the TCR and CD28-dependent costimulation. Accordingly, blockade of the CD28-costimulatory pathway abrogates the capacity of agonistic anti-4-1BB Ab to trigger Th-independent CTL immunity. In conclusion, our data reveal that the 4-1BB-mediated survival signal is positioned downstream of Ag-specific TCR triggering and CD28-dependent costimulation of naive CTL. The powerful effects of 4-1BB triggering on the induction, amplification, and persistence of CTL responses provide a novel strategy for increasing the potency of vaccines against cancers.

Authors+Show Affiliations

Department of Immunohematology and Bloodtransfusion, Leiden University Medical Center, Leiden, The Netherlands.No affiliation info availableNo affiliation info availableNo 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

Language

eng

PubMed ID

11937526

Citation

Diehl, Linda, et al. "In Vivo Triggering Through 4-1BB Enables Th-independent Priming of CTL in the Presence of an Intact CD28 Costimulatory Pathway." Journal of Immunology (Baltimore, Md. : 1950), vol. 168, no. 8, 2002, pp. 3755-62.
Diehl L, van Mierlo GJ, den Boer AT, et al. In vivo triggering through 4-1BB enables Th-independent priming of CTL in the presence of an intact CD28 costimulatory pathway. J Immunol. 2002;168(8):3755-62.
Diehl, L., van Mierlo, G. J., den Boer, A. T., van der Voort, E., Fransen, M., van Bostelen, L., Krimpenfort, P., Melief, C. J., Mittler, R., Toes, R. E., & Offringa, R. (2002). In vivo triggering through 4-1BB enables Th-independent priming of CTL in the presence of an intact CD28 costimulatory pathway. Journal of Immunology (Baltimore, Md. : 1950), 168(8), 3755-62.
Diehl L, et al. In Vivo Triggering Through 4-1BB Enables Th-independent Priming of CTL in the Presence of an Intact CD28 Costimulatory Pathway. J Immunol. 2002 Apr 15;168(8):3755-62. PubMed PMID: 11937526.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In vivo triggering through 4-1BB enables Th-independent priming of CTL in the presence of an intact CD28 costimulatory pathway. AU - Diehl,Linda, AU - van Mierlo,Geertje J D, AU - den Boer,Annemieke T, AU - van der Voort,Ellen, AU - Fransen,Marieke, AU - van Bostelen,Liesbeth, AU - Krimpenfort,Paul, AU - Melief,Cornelis J M, AU - Mittler,Robert, AU - Toes,Rene E M, AU - Offringa,Rienk, PY - 2002/4/9/pubmed PY - 2002/5/25/medline PY - 2002/4/9/entrez SP - 3755 EP - 62 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J. Immunol. VL - 168 IS - 8 N2 - Triggering of 4-1BB, a member of the TNFR family, through in vivo administration of agonistic anti-4-1BB Ab delivers a powerful costimulatory signal to CTL. We found this signal to effectively replace the need for CD4(+) T cell help in the cross-priming of tumor-specific CTL immunity. Furthermore, 4-1BB Ab can convert an otherwise tolerogenic peptide vaccine into a formulation capable of efficient CTL priming. Initial activation of naive CTL can occur in the absence of 4-1BB costimulation, but this signal permits increased survival of Ag-stimulated CTL. Because naive CTL do not express 4-1BB at their surface, susceptibility to 4-1BB triggering depends on prior up-regulation of this receptor. We show that this requires both stimulation of the TCR and CD28-dependent costimulation. Accordingly, blockade of the CD28-costimulatory pathway abrogates the capacity of agonistic anti-4-1BB Ab to trigger Th-independent CTL immunity. In conclusion, our data reveal that the 4-1BB-mediated survival signal is positioned downstream of Ag-specific TCR triggering and CD28-dependent costimulation of naive CTL. The powerful effects of 4-1BB triggering on the induction, amplification, and persistence of CTL responses provide a novel strategy for increasing the potency of vaccines against cancers. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/11937526/In_vivo_triggering_through_4_1BB_enables_Th_independent_priming_of_CTL_in_the_presence_of_an_intact_CD28_costimulatory_pathway_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=11937526 DB - PRIME DP - Unbound Medicine ER -