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A switch in costimulation from CD28 to 4-1BB during primary versus secondary CD8 T cell response to influenza in vivo.
J Immunol. 2004 Jan 15; 172(2):981-8.JI

Abstract

4-1BBL(-/-) mice exhibit normal primary CD8 T cell responses to influenza virus, but show decreased CD8 T cell numbers late in the primary response as well as decreased secondary responses. In contrast, CD28(-/-) mice are defective in initial CD8 T cell expansion. Using agonistic anti-4-1BB Ab to replace the CD28 or 4-1BB signal, we examined the timing of the required signals for CD28 vs 4-1BB costimulation. A single dose of agonistic anti-4-1BB Ab added only during priming restores the secondary CD8 T cell response in CD28(-/-) mice. Once the T cell numbers in the primary response reach a minimum threshold, a full secondary response is achieved even in the absence of CD28. In contrast, anti-4-1BB added during priming fails to correct the defective secondary response in 4-1BBL(-/-) mice, whereas addition of anti-4-1BB during challenge fully restores this response. Thus, there is a switch in costimulatory requirement from CD28 to 4-1BB during primary vs recall responses. Adoptive transfer studies show that T cells primed in 4-1BBL(-/-) or wild-type mice are equally capable of re-expansion when rechallenged in wild-type mice. These studies rule out a model in which signals delivered through 4-1BB during priming program the T cells to give a full recall response and suggest that 4-1BB-4-1BBL interactions take place at later stages in the immune response. The results indicate that anti-4-1BB or 4-1BBL therapy will be most effective during the boost phase of a prime-boost vaccination strategy.

Authors+Show Affiliations

Department of Immunology, University of Toronto, Toronto, Ontario, Canada M5S 1A8.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

14707071

Citation

Bertram, Edward M., et al. "A Switch in Costimulation From CD28 to 4-1BB During Primary Versus Secondary CD8 T Cell Response to Influenza in Vivo." Journal of Immunology (Baltimore, Md. : 1950), vol. 172, no. 2, 2004, pp. 981-8.
Bertram EM, Dawicki W, Sedgmen B, et al. A switch in costimulation from CD28 to 4-1BB during primary versus secondary CD8 T cell response to influenza in vivo. J Immunol. 2004;172(2):981-8.
Bertram, E. M., Dawicki, W., Sedgmen, B., Bramson, J. L., Lynch, D. H., & Watts, T. H. (2004). A switch in costimulation from CD28 to 4-1BB during primary versus secondary CD8 T cell response to influenza in vivo. Journal of Immunology (Baltimore, Md. : 1950), 172(2), 981-8.
Bertram EM, et al. A Switch in Costimulation From CD28 to 4-1BB During Primary Versus Secondary CD8 T Cell Response to Influenza in Vivo. J Immunol. 2004 Jan 15;172(2):981-8. PubMed PMID: 14707071.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A switch in costimulation from CD28 to 4-1BB during primary versus secondary CD8 T cell response to influenza in vivo. AU - Bertram,Edward M, AU - Dawicki,Wojciech, AU - Sedgmen,Bradley, AU - Bramson,Jonathan L, AU - Lynch,David H, AU - Watts,Tania H, PY - 2004/1/7/pubmed PY - 2004/4/21/medline PY - 2004/1/7/entrez SP - 981 EP - 8 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J. Immunol. VL - 172 IS - 2 N2 - 4-1BBL(-/-) mice exhibit normal primary CD8 T cell responses to influenza virus, but show decreased CD8 T cell numbers late in the primary response as well as decreased secondary responses. In contrast, CD28(-/-) mice are defective in initial CD8 T cell expansion. Using agonistic anti-4-1BB Ab to replace the CD28 or 4-1BB signal, we examined the timing of the required signals for CD28 vs 4-1BB costimulation. A single dose of agonistic anti-4-1BB Ab added only during priming restores the secondary CD8 T cell response in CD28(-/-) mice. Once the T cell numbers in the primary response reach a minimum threshold, a full secondary response is achieved even in the absence of CD28. In contrast, anti-4-1BB added during priming fails to correct the defective secondary response in 4-1BBL(-/-) mice, whereas addition of anti-4-1BB during challenge fully restores this response. Thus, there is a switch in costimulatory requirement from CD28 to 4-1BB during primary vs recall responses. Adoptive transfer studies show that T cells primed in 4-1BBL(-/-) or wild-type mice are equally capable of re-expansion when rechallenged in wild-type mice. These studies rule out a model in which signals delivered through 4-1BB during priming program the T cells to give a full recall response and suggest that 4-1BB-4-1BBL interactions take place at later stages in the immune response. The results indicate that anti-4-1BB or 4-1BBL therapy will be most effective during the boost phase of a prime-boost vaccination strategy. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/14707071/A_switch_in_costimulation_from_CD28_to_4_1BB_during_primary_versus_secondary_CD8_T_cell_response_to_influenza_in_vivo_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=14707071 DB - PRIME DP - Unbound Medicine ER -