Tripartite motif-containing protein 30 modulates TCR-activated proliferation and effector functions in CD4+ T cells

PLoS One. 2014 Apr 22;9(4):e95805. doi: 10.1371/journal.pone.0095805. eCollection 2014.

Abstract

To avoid excessive activation, immune signals are tightly controlled by diverse inhibitory proteins. TRIM30, a tripartite motif (TRIM)-containing protein is one of such inhibitors known to function in macrophages. To define the roles of TRIM30, we generated Trim30 knockout (Trim30-/-) mice. Trim30 deletion caused no major developmental defects in any organs, nor showed any discernable defect in the activation of macrophages. But, Trim30-/- mice showed increased CD4/CD8 ratio when aged and Trim30-/- CD4+ T cells exhibited an abnormal response upon TCR activation, in particular in the absence of a costimulatory signal. Adoptive transfer of wild-type and Trim30-/- CD4+ T cells together into lymphopenic hosts confirmed higher proliferation of the Trim30-/- CD4+ T cells in vivo. Despite the enhanced proliferation, Trim30-/- T cells showed decreased levels of NF-κB activation and IL-2 production compared to wild-type cells. These results indicate a distinct requirement for TRIM30 in modulation of NF-κB activation and cell proliferation induced by TCR stimulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • CD4-CD8 Ratio
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism*
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • Cell Cycle / genetics
  • Homeodomain Proteins / genetics
  • Lymphocyte Activation / genetics*
  • Lymphocyte Activation / immunology*
  • Male
  • Mice
  • Mice, Knockout
  • NF-kappa B / metabolism
  • Receptors, Antigen, T-Cell / metabolism*

Substances

  • Carrier Proteins
  • Homeodomain Proteins
  • NF-kappa B
  • Receptors, Antigen, T-Cell
  • TRIM3 protein, mouse
  • RAG-1 protein