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Potential role of 4-1BB in T cell activation. Comparison with the costimulatory molecule CD28.
J Immunol. 1995 Oct 01; 155(7):3360-7.JI

Abstract

The expression of the murine T cell Ag 4-1BB, a member of the TNF-R family, is induced by T cell activation. Previously, we and others had shown that signaling through 4-1BB enhanced proliferative T cell responses. To investigate a potential role for the interaction of 4-1BB with its ligand (4-1BBL) in T cell activation, we studied the ability of a soluble chimera of 4-1BB (4-1BBFc) to interfere with proliferative responses and cytokine production in models of activation dependent in intercellular interactions. The potential blocking effect of 4-1BBFc was compared with that of the chimeric molecule CTLA-4Ig, a reagent known to interfere with the interaction of CD28 (and/or CTLA-4) with B7 costimulatory receptors. In this study, we report that 4-1BBFc partially blocked both the activation of unfractionated splenocytes triggered by soluble anti-CD3 (anti-CD3s), and the more physiologically relevant responses to alloantigen. In addition, we show that both chimeric molecules partially blocked proliferative responses and IL-2 secretion by highly purified resting T cells activated with anti-CD3s in the presence of fixed accessory cells that express B7 receptors and 4-1BBL. Furthermore, in this model system, the blocking capacity of 4-1BBFc and CTLA-4Ig appears to correlate with the relative expression of their respective cognate receptors (4-1BBL and B7) on the accessory cell. Simultaneous addition of both blocking reagents produced an additive effect in the model systems studied.

Authors+Show Affiliations

Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis 46202, USA.No 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
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

7561030

Citation

Hurtado, J C., et al. "Potential Role of 4-1BB in T Cell Activation. Comparison With the Costimulatory Molecule CD28." Journal of Immunology (Baltimore, Md. : 1950), vol. 155, no. 7, 1995, pp. 3360-7.
Hurtado JC, Kim SH, Pollok KE, et al. Potential role of 4-1BB in T cell activation. Comparison with the costimulatory molecule CD28. J Immunol. 1995;155(7):3360-7.
Hurtado, J. C., Kim, S. H., Pollok, K. E., Lee, Z. H., & Kwon, B. S. (1995). Potential role of 4-1BB in T cell activation. Comparison with the costimulatory molecule CD28. Journal of Immunology (Baltimore, Md. : 1950), 155(7), 3360-7.
Hurtado JC, et al. Potential Role of 4-1BB in T Cell Activation. Comparison With the Costimulatory Molecule CD28. J Immunol. 1995 Oct 1;155(7):3360-7. PubMed PMID: 7561030.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Potential role of 4-1BB in T cell activation. Comparison with the costimulatory molecule CD28. AU - Hurtado,J C, AU - Kim,S H, AU - Pollok,K E, AU - Lee,Z H, AU - Kwon,B S, PY - 1995/10/1/pubmed PY - 1995/10/1/medline PY - 1995/10/1/entrez SP - 3360 EP - 7 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J. Immunol. VL - 155 IS - 7 N2 - The expression of the murine T cell Ag 4-1BB, a member of the TNF-R family, is induced by T cell activation. Previously, we and others had shown that signaling through 4-1BB enhanced proliferative T cell responses. To investigate a potential role for the interaction of 4-1BB with its ligand (4-1BBL) in T cell activation, we studied the ability of a soluble chimera of 4-1BB (4-1BBFc) to interfere with proliferative responses and cytokine production in models of activation dependent in intercellular interactions. The potential blocking effect of 4-1BBFc was compared with that of the chimeric molecule CTLA-4Ig, a reagent known to interfere with the interaction of CD28 (and/or CTLA-4) with B7 costimulatory receptors. In this study, we report that 4-1BBFc partially blocked both the activation of unfractionated splenocytes triggered by soluble anti-CD3 (anti-CD3s), and the more physiologically relevant responses to alloantigen. In addition, we show that both chimeric molecules partially blocked proliferative responses and IL-2 secretion by highly purified resting T cells activated with anti-CD3s in the presence of fixed accessory cells that express B7 receptors and 4-1BBL. Furthermore, in this model system, the blocking capacity of 4-1BBFc and CTLA-4Ig appears to correlate with the relative expression of their respective cognate receptors (4-1BBL and B7) on the accessory cell. Simultaneous addition of both blocking reagents produced an additive effect in the model systems studied. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/7561030/Potential_role_of_4_1BB_in_T_cell_activation__Comparison_with_the_costimulatory_molecule_CD28_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=7561030 DB - PRIME DP - Unbound Medicine ER -