TcR-induced regulated secretion leads to surface expression of CTLA-4 in CD4+CD25+ T cells

Immunology. 2008 Sep;125(1):70-9. doi: 10.1111/j.1365-2567.2008.02822.x. Epub 2008 Apr 4.

Abstract

In this study we show that CD4+ T cells develop a functional regulated secretory compartment after differentiation into effector cells, as shown by their increased expression and T-cell receptor-induced exocytosis of lysosomal and cytotoxic effector proteins. We tested the hypothesis that activation-induced surface cytotoxic T-lymphocyte-associated antigen (CTLA-4) expression in CD4+CD25+ regulatory T cells occurs via a similar regulated secretory pathway. Fluorescence microscopy showed that internal CTLA-4 in these cells was stored in a vesicular compartment distinct from lysosomal vesicles. Rapid activation-induced CTLA-4 surface expression in mouse CD4+CD25+ T cells is independent of protein synthesis and Rab-27a. When antigen-dependent T-cell-antigen-presenting cell (APC) conjugates were analysed for surface distribution of CD86 on APC, a higher concentration of CD86 molecules was observed in the synapse of APC conjugated to CD4+CD25+ cells than APC conjugated to CD4+CD25- cells. These results demonstrate that fast delivery of mediators by the regulated secretory pathway in CD4+ T cells can be used to perform other functions that are not involved in cytotoxic function but that can influence/regulate other cells.

MeSH terms

  • Animals
  • Antigen-Presenting Cells / immunology
  • Antigens, CD / metabolism*
  • B7-2 Antigen / metabolism
  • CD8-Positive T-Lymphocytes / immunology
  • CTLA-4 Antigen
  • Cells, Cultured
  • Exocytosis / immunology
  • Humans
  • Lymph Nodes / immunology
  • Lymphocyte Activation / immunology
  • Lysosomes / immunology
  • Mice
  • Receptors, Antigen, T-Cell / immunology*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocytes, Regulatory / immunology*
  • rab GTP-Binding Proteins / immunology
  • rab27 GTP-Binding Proteins

Substances

  • Antigens, CD
  • B7-2 Antigen
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Cd86 protein, mouse
  • Ctla4 protein, mouse
  • Receptors, Antigen, T-Cell
  • rab27 GTP-Binding Proteins
  • Rab27a protein, mouse
  • rab GTP-Binding Proteins