4-1BB Cross-Linking Enhances the Survival and Cell Cycle Progression of CD4 T Lymphocytes

Cell Immunol. 2003 Jun;223(2):143-50. doi: 10.1016/s0008-8749(03)00169-2.

Abstract

4-1BB, a T cell co-stimulatory receptor, prolongs the survival and multiplication of CD4 T cells. Cross-linking 4-1BB stimulated expression of the anti-apoptotic genes bcl-XL and bcl-2, as well as of cyclins D2 and E, and inhibited expression of the cyclin-dependent kinase (cdk) inhibitor p27kip1. Ova-activated CD4 T cells of 4-1BB-deficient/DO11.10 TCR transgenic mice survived less well and underwent less expansion than cells of wild type DO11.10 TCR transgenic mice. These findings demonstrate that 4-1BB is a co-stimulatory molecule for CD4 T cell survival and expansion in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD
  • Blotting, Western
  • CD4-Positive T-Lymphocytes / physiology*
  • Cell Cycle / physiology
  • Cell Cycle Proteins / biosynthesis
  • Cell Cycle Proteins / drug effects
  • Cell Survival / physiology
  • Cross-Linking Reagents / pharmacology
  • Cyclin D2
  • Cyclin E / biosynthesis
  • Cyclin E / drug effects
  • Cyclin-Dependent Kinase Inhibitor p27
  • Cyclins / biosynthesis
  • Cyclins / drug effects
  • Flow Cytometry
  • Gene Expression Regulation / immunology
  • Genes, bcl-2 / drug effects
  • Genes, bcl-2 / physiology
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / physiology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Transgenic
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis
  • Proto-Oncogene Proteins c-bcl-2 / drug effects
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • RNA, Messenger / analysis
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Nerve Growth Factor / deficiency
  • Receptors, Nerve Growth Factor / drug effects
  • Receptors, Nerve Growth Factor / genetics
  • Receptors, Nerve Growth Factor / metabolism*
  • Receptors, Tumor Necrosis Factor / deficiency
  • Receptors, Tumor Necrosis Factor / drug effects
  • Receptors, Tumor Necrosis Factor / genetics
  • Receptors, Tumor Necrosis Factor / metabolism*
  • T-Lymphocyte Subsets / physiology*
  • Tumor Necrosis Factor Receptor Superfamily, Member 9
  • Tumor Suppressor Proteins / biosynthesis
  • Tumor Suppressor Proteins / drug effects
  • bcl-X Protein

Substances

  • Antigens, CD
  • Bcl2l1 protein, mouse
  • Ccnd2 protein, mouse
  • Cdkn1b protein, mouse
  • Cell Cycle Proteins
  • Cross-Linking Reagents
  • Cyclin D2
  • Cyclin E
  • Cyclins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • Receptors, Antigen, T-Cell
  • Receptors, Nerve Growth Factor
  • Receptors, Tumor Necrosis Factor
  • Tnfrsf9 protein, mouse
  • Tumor Necrosis Factor Receptor Superfamily, Member 9
  • Tumor Suppressor Proteins
  • bcl-X Protein
  • Cyclin-Dependent Kinase Inhibitor p27