Premium
Activated CD4 + CD25 + T cells suppress antigen‐specific CD4 + and CD8 + T cells but induce a suppressive phenotype only in CD4 + T cells
Author(s) -
Dieckmann Detlef,
Plöttner Heidi,
Dotterweich Stefanie,
Schuler Gerold
Publication year - 2005
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2005.02144.x
Subject(s) - il 2 receptor , interleukin 21 , cytotoxic t cell , biology , cd8 , antigen presenting cell , interleukin 3 , cytokine , microbiology and biotechnology , antigen , immune system , t cell , interleukin 12 , natural killer t cell , immunology , in vitro , biochemistry
Summary CD4 + CD25 + regulatory T cells are increasingly recognized as central players in the regulation of immune responses. In vitro studies have mostly employed allogeneic or polyclonal responses to monitor suppression. Little is known about the ability of CD4 + CD25 + regulatory T cells to suppress antigen‐specific immune responses in humans. It has been previously shown that CD4 + CD25 + regulatory T cells anergize CD4 + T cells and turn them into suppressor T cells. In the present study we demonstrate for the first time in humans that CD4 + CD25 + T cells are able to inhibit the proliferation and cytokine production of antigen specific CD4 + and CD8 + T cells. This suppression only occurs when CD4 + CD25 + T cells are preactivated. Furthermore, we could demonstrate that CD4 + T‐cell clones stop secreting interferon‐γ (IFN‐γ), start to produce interleukin‐10 and transforming growth factor‐β after coculture with preactivated CD4 + CD25 + T cells and become suppressive themselves. Surprisingly preactivated CD4 + CD25 + T cells affect CD8 + T cells differently, leading to reduced proliferation and reduced production of IFN‐γ. This effect is sustained and cannot be reverted by exogenous interleukin‐2. Yet CD8 + T cells, unlike CD4 + T cells do not start to produce immunoregulatory cytokines and do not become suppressive after coculture with CD4 + CD25 + T cells.