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4-1BB and OX40 stimulation enhance CD8 and CD4 T-cell responses to a DNA prime, poxvirus boost vaccine.
Immunology. 2004 Aug; 112(4):559-66.I

Abstract

4-1BB (CD137) is a tumour necrosis factor receptor (TNFR) family member, expressed primarily on CD8 T cells after activation. Signalling through 4-1BB has been reported to enhance CD8 T-cell expansion and to protect activated CD8 T cells from death, resulting in an enlarged memory population. Although stimulating 4-1BB has been shown to significantly improve the immune response to weak immunogens such as tumours, little is known about its effect on the CD8 T-cell response to a powerful viral vector such as vaccinia. To test 4-1BB's ability to improve the murine CD8 T cell response to a DNA prime, poxvirus boost vaccine, similar to those used for human immunodeficiency virus and simian immunodeficiency virus vaccines, we administered 4-1BB agonist antibody at the time of the poxvirus boost. 4-1BB stimulation increased the number of functional memory CD8 T cells by two- to fourfold. However, we saw a similar enhancement at the peak of the response and in the memory phase, thus we found no evidence in the context of virus infection that 4-1BB stimulation could increase the percentage of CD8 T cells that survive the acute activation phase to become memory cells. OX40 (CD134) is an analogous TNFR family member expressed primarily on activated CD4 T cells. OX40 stimulation increased the number of antigen-specific CD4 T cells approximately threefold. Stimulating both 4-1BB and OX40 enhanced the CD8 T-cell response more than 4-1BB alone. Thus stimulating these receptors can improve the response to a powerful virus vector, and may be useful in vaccine development.

Authors+Show Affiliations

Department of Molecular Microbiology and Immunology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, 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

Language

eng

PubMed ID

15270726

Citation

Munks, Michael W., et al. "4-1BB and OX40 Stimulation Enhance CD8 and CD4 T-cell Responses to a DNA Prime, Poxvirus Boost Vaccine." Immunology, vol. 112, no. 4, 2004, pp. 559-66.
Munks MW, Mourich DV, Mittler RS, et al. 4-1BB and OX40 stimulation enhance CD8 and CD4 T-cell responses to a DNA prime, poxvirus boost vaccine. Immunology. 2004;112(4):559-66.
Munks, M. W., Mourich, D. V., Mittler, R. S., Weinberg, A. D., & Hill, A. B. (2004). 4-1BB and OX40 stimulation enhance CD8 and CD4 T-cell responses to a DNA prime, poxvirus boost vaccine. Immunology, 112(4), 559-66.
Munks MW, et al. 4-1BB and OX40 Stimulation Enhance CD8 and CD4 T-cell Responses to a DNA Prime, Poxvirus Boost Vaccine. Immunology. 2004;112(4):559-66. PubMed PMID: 15270726.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 4-1BB and OX40 stimulation enhance CD8 and CD4 T-cell responses to a DNA prime, poxvirus boost vaccine. AU - Munks,Michael W, AU - Mourich,Dan V, AU - Mittler,Robert S, AU - Weinberg,Andrew D, AU - Hill,Ann B, PY - 2004/7/24/pubmed PY - 2004/9/21/medline PY - 2004/7/24/entrez SP - 559 EP - 66 JF - Immunology JO - Immunology VL - 112 IS - 4 N2 - 4-1BB (CD137) is a tumour necrosis factor receptor (TNFR) family member, expressed primarily on CD8 T cells after activation. Signalling through 4-1BB has been reported to enhance CD8 T-cell expansion and to protect activated CD8 T cells from death, resulting in an enlarged memory population. Although stimulating 4-1BB has been shown to significantly improve the immune response to weak immunogens such as tumours, little is known about its effect on the CD8 T-cell response to a powerful viral vector such as vaccinia. To test 4-1BB's ability to improve the murine CD8 T cell response to a DNA prime, poxvirus boost vaccine, similar to those used for human immunodeficiency virus and simian immunodeficiency virus vaccines, we administered 4-1BB agonist antibody at the time of the poxvirus boost. 4-1BB stimulation increased the number of functional memory CD8 T cells by two- to fourfold. However, we saw a similar enhancement at the peak of the response and in the memory phase, thus we found no evidence in the context of virus infection that 4-1BB stimulation could increase the percentage of CD8 T cells that survive the acute activation phase to become memory cells. OX40 (CD134) is an analogous TNFR family member expressed primarily on activated CD4 T cells. OX40 stimulation increased the number of antigen-specific CD4 T cells approximately threefold. Stimulating both 4-1BB and OX40 enhanced the CD8 T-cell response more than 4-1BB alone. Thus stimulating these receptors can improve the response to a powerful virus vector, and may be useful in vaccine development. SN - 0019-2805 UR - https://www.unboundmedicine.com/medline/citation/15270726/4_1BB_and_OX40_stimulation_enhance_CD8_and_CD4_T_cell_responses_to_a_DNA_prime_poxvirus_boost_vaccine_ L2 - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=linkout&SEARCH=15270726.ui DB - PRIME DP - Unbound Medicine ER -