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4-1BB and OX40 act independently to facilitate robust CD8 and CD4 recall responses.
J Immunol. 2004 Nov 15; 173(10):5944-51.JI

Abstract

Mice deficient in OX40 or 4-1BB costimulatory pathways show defects in T cell recall responses, with predominant effects on CD4 vs CD8 T cells, respectively. However, OX40L can also stimulate CD8 T cells and 4-1BBL can influence CD4 T cells, raising the possibility of redundancy between the two TNFR family costimulators. To test this possibility, we generated mice deficient in both 4-1BBL and OX40L. In an adoptive transfer model, CD4 T cells expressed 4-1BB and OX40 sequentially in response to immunization, with little or no overlap in the timing of their expression. Under the same conditions, CD8 T cells expressed 4-1BB, but no detectable OX40. Thus, in vivo expression of 4-1BB and OX40 can be temporally and spatially segregated. In the absence of OX40L, there were decreased CD4 T cells late in the primary response and no detectable secondary expansion of adoptively transferred CD4 T cells under conditions in which primary expansion was unaffected. The 4-1BBL had a minor effect on the primary response of CD4 T cells in this model, but showed larger effects on the secondary response, although 4-1BBL(-/-) mice show less impairment in CD4 secondary responses than OX40L(-/-) mice. The 4-1BBL(-/-) and double knockout mice were similarly impaired in the CD8 T cell response, whereas OX40L(-/-) and double knockout mice were similarly impaired in the CD4 T cell response to both protein Ag and influenza virus. Thus, 4-1BB and OX40 act independently and nonredundantly to facilitate robust CD4 and CD8 recall responses.

Authors+Show Affiliations

Department of Immunology, University of Toronto, 1 King's College Circle, Toronto, Ontario, Canada.No 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

15528328

Citation

Dawicki, Wojciech, et al. "4-1BB and OX40 Act Independently to Facilitate Robust CD8 and CD4 Recall Responses." Journal of Immunology (Baltimore, Md. : 1950), vol. 173, no. 10, 2004, pp. 5944-51.
Dawicki W, Bertram EM, Sharpe AH, et al. 4-1BB and OX40 act independently to facilitate robust CD8 and CD4 recall responses. J Immunol. 2004;173(10):5944-51.
Dawicki, W., Bertram, E. M., Sharpe, A. H., & Watts, T. H. (2004). 4-1BB and OX40 act independently to facilitate robust CD8 and CD4 recall responses. Journal of Immunology (Baltimore, Md. : 1950), 173(10), 5944-51.
Dawicki W, et al. 4-1BB and OX40 Act Independently to Facilitate Robust CD8 and CD4 Recall Responses. J Immunol. 2004 Nov 15;173(10):5944-51. PubMed PMID: 15528328.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 4-1BB and OX40 act independently to facilitate robust CD8 and CD4 recall responses. AU - Dawicki,Wojciech, AU - Bertram,Edward M, AU - Sharpe,Arlene H, AU - Watts,Tania H, PY - 2004/11/6/pubmed PY - 2004/12/18/medline PY - 2004/11/6/entrez SP - 5944 EP - 51 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J. Immunol. VL - 173 IS - 10 N2 - Mice deficient in OX40 or 4-1BB costimulatory pathways show defects in T cell recall responses, with predominant effects on CD4 vs CD8 T cells, respectively. However, OX40L can also stimulate CD8 T cells and 4-1BBL can influence CD4 T cells, raising the possibility of redundancy between the two TNFR family costimulators. To test this possibility, we generated mice deficient in both 4-1BBL and OX40L. In an adoptive transfer model, CD4 T cells expressed 4-1BB and OX40 sequentially in response to immunization, with little or no overlap in the timing of their expression. Under the same conditions, CD8 T cells expressed 4-1BB, but no detectable OX40. Thus, in vivo expression of 4-1BB and OX40 can be temporally and spatially segregated. In the absence of OX40L, there were decreased CD4 T cells late in the primary response and no detectable secondary expansion of adoptively transferred CD4 T cells under conditions in which primary expansion was unaffected. The 4-1BBL had a minor effect on the primary response of CD4 T cells in this model, but showed larger effects on the secondary response, although 4-1BBL(-/-) mice show less impairment in CD4 secondary responses than OX40L(-/-) mice. The 4-1BBL(-/-) and double knockout mice were similarly impaired in the CD8 T cell response, whereas OX40L(-/-) and double knockout mice were similarly impaired in the CD4 T cell response to both protein Ag and influenza virus. Thus, 4-1BB and OX40 act independently and nonredundantly to facilitate robust CD4 and CD8 recall responses. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/15528328/4_1BB_and_OX40_act_independently_to_facilitate_robust_CD8_and_CD4_recall_responses_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=15528328 DB - PRIME DP - Unbound Medicine ER -