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

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.

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