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Large‐scale expansion of rat CD4 + CD25 + T reg cells in the absence of T‐cell receptor stimulation
Author(s) -
Beyersdorf Niklas,
Balbach Karen,
Hünig Thomas,
Kerkau Thomas
Publication year - 2006
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.1365-2567.2006.02455.x
Subject(s) - cd28 , t cell receptor , il 2 receptor , t cell , biology , stimulation , microbiology and biotechnology , monoclonal antibody , interleukin 2 , in vitro , antibody , immunology , endocrinology , immune system , biochemistry
Summary T‐cell receptor (TCR) stimulation is both central to homeostatic maintenance of CD4 + CD25 + regulatory T cells (T reg cells) in vivo and a prerequisite for the initiation of suppression by T reg cells, both in vivo and in vitro . However, TCR‐independent stimulation of T reg cells, e.g. with superagonistic CD28‐specific monoclonal antibodies (CD28‐SA), not only expands these cells in vivo but, as we show here, also mediates large‐scale expansion of rat T reg cells in vitro. Interestingly, CD28‐SA stimulation plus interleukin (IL)‐2 was even superior to conventional costimulation plus IL‐2 in promoting T reg cell growth in vitro. Despite their highly activated phenotype suppression by T reg cells expanded in the absence of TCR stimulation remained fully dependent on TCR‐triggering for initiation and cell contact was required to exert suppression. With regard to the regulation of suppression by CD28 stimulation we observed that neither the presence of a conventional anti‐CD28 monoclonal antibody nor a CD28‐SA generally rendered conventional T cells resistant to suppression by preactivated T reg cells. Taken together, we provide a novel protocol for long‐term propagation of T reg cells in vitro and our data are the first to reveal a difference in the signals required for activation and expansion of T reg cells and those, involving the TCR, necessary for the initiation of suppression.