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Differential expression and costimulatory effect of 4-1BB (CD137) and CD28 molecules on cytokine-induced murine CD8(+) Tc1 and Tc2 cells.
Cell Immunol. 1999 Feb 25; 192(1):63-71.CI

Abstract

In this study we report that the relative expression of 4-1BB (CD137) and CD28 molecules can differentially be modulated on CD8(+) T cells by combinations of various cytokines and anti-cytokine antibodies. During allostimulation of naive CD8(+) T cells in the presence of IL-2, IFN-gamma, IL-12, and anti-IL-4, they evolved into IL-2, IFN-gamma-producing Tc1 cells and showed inability to upregulate 4-1BB expression but not CD28. On the other hand, the Tc2 cells, generated in the presence of allogeneic APCs, IL-2, IL-10, IL-4, and anti-IFN-gamma, demonstrated intact and elevated 4-1BB and CD28 molecules. Activation of Tc1 and Tc2 cells with anti-CD3 and plate-bound anti-4-1BB and anti-CD28 mAbs revealed differential proliferative and cytokine secretory patterns. The 4-1BB signaling in the context of anti-CD3 as first signal led to the increased secretion of IL-4 by the Tc2 cells and not by Tc1 cells, while CD28 triggering produced IL-4 from Tc2 and IL-2 and IFN-gamma from Tc1 cells. Flow cytometric analysis of cell surface expression on Tc1 and Tc2 cells strengthened our observation that 4-1BB expression but not CD28 is poorly expressed on Tc1 cells. Both of the polarized CD8(+) T cell subsets exhibited comparable cytotoxic abilities and perforin and granzyme expression. The regeneration of 4-1BB expression is possible on Tc1 cells when back cultured in a Tc2 cytokine environment, but its expression could not be significantly altered on the Tc2 population unless IL-12 was included in the system.

Authors+Show Affiliations

Department of Microbiology and Immunology and Walther Oncology Center, Indiana University School of Medicine, 635 Barnhill Drive, Indianapolis, Indiana 46202, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10066348

Citation

Vinay, D S., and B S. Kwon. "Differential Expression and Costimulatory Effect of 4-1BB (CD137) and CD28 Molecules On Cytokine-induced Murine CD8(+) Tc1 and Tc2 Cells." Cellular Immunology, vol. 192, no. 1, 1999, pp. 63-71.
Vinay DS, Kwon BS. Differential expression and costimulatory effect of 4-1BB (CD137) and CD28 molecules on cytokine-induced murine CD8(+) Tc1 and Tc2 cells. Cell Immunol. 1999;192(1):63-71.
Vinay, D. S., & Kwon, B. S. (1999). Differential expression and costimulatory effect of 4-1BB (CD137) and CD28 molecules on cytokine-induced murine CD8(+) Tc1 and Tc2 cells. Cellular Immunology, 192(1), 63-71.
Vinay DS, Kwon BS. Differential Expression and Costimulatory Effect of 4-1BB (CD137) and CD28 Molecules On Cytokine-induced Murine CD8(+) Tc1 and Tc2 Cells. Cell Immunol. 1999 Feb 25;192(1):63-71. PubMed PMID: 10066348.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential expression and costimulatory effect of 4-1BB (CD137) and CD28 molecules on cytokine-induced murine CD8(+) Tc1 and Tc2 cells. AU - Vinay,D S, AU - Kwon,B S, PY - 1999/3/6/pubmed PY - 1999/3/6/medline PY - 1999/3/6/entrez SP - 63 EP - 71 JF - Cellular immunology JO - Cell. Immunol. VL - 192 IS - 1 N2 - In this study we report that the relative expression of 4-1BB (CD137) and CD28 molecules can differentially be modulated on CD8(+) T cells by combinations of various cytokines and anti-cytokine antibodies. During allostimulation of naive CD8(+) T cells in the presence of IL-2, IFN-gamma, IL-12, and anti-IL-4, they evolved into IL-2, IFN-gamma-producing Tc1 cells and showed inability to upregulate 4-1BB expression but not CD28. On the other hand, the Tc2 cells, generated in the presence of allogeneic APCs, IL-2, IL-10, IL-4, and anti-IFN-gamma, demonstrated intact and elevated 4-1BB and CD28 molecules. Activation of Tc1 and Tc2 cells with anti-CD3 and plate-bound anti-4-1BB and anti-CD28 mAbs revealed differential proliferative and cytokine secretory patterns. The 4-1BB signaling in the context of anti-CD3 as first signal led to the increased secretion of IL-4 by the Tc2 cells and not by Tc1 cells, while CD28 triggering produced IL-4 from Tc2 and IL-2 and IFN-gamma from Tc1 cells. Flow cytometric analysis of cell surface expression on Tc1 and Tc2 cells strengthened our observation that 4-1BB expression but not CD28 is poorly expressed on Tc1 cells. Both of the polarized CD8(+) T cell subsets exhibited comparable cytotoxic abilities and perforin and granzyme expression. The regeneration of 4-1BB expression is possible on Tc1 cells when back cultured in a Tc2 cytokine environment, but its expression could not be significantly altered on the Tc2 population unless IL-12 was included in the system. SN - 0008-8749 UR - https://www.unboundmedicine.com/medline/citation/10066348/Differential_expression_and_costimulatory_effect_of_4_1BB__CD137__and_CD28_molecules_on_cytokine_induced_murine_CD8_+__Tc1_and_Tc2_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0008-8749(98)91433-2 DB - PRIME DP - Unbound Medicine ER -