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Everolimus and Basiliximab Permit Suppression by Human CD4 + CD25 + Cells in vitro
Author(s) -
Game David S.,
HernandezFuentes Maria P.,
Lechler Robert I.
Publication year - 2005
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2005.00758.x
Subject(s) - basiliximab , medicine , everolimus , in vitro , pharmacology , transplantation , kidney transplantation , genetics , biology
Immunosuppressive drugs are essential for the prevention of acute transplant rejection but some may not promote long‐term tolerance. Tolerance is dependent on the presence and regulatory function of CD4 + CD25 + T cells in a number of animal models. The direct effects of immunosuppressive drugs on CD4 + CD25 + cells, particularly those that interfere with IL‐2 signaling are uncertain. We studied the effects of the rapamycin derivative everolimus and the anti‐CD25 monoclonal antibody basiliximab on the regulatory capacity of human CD4 + CD25 + cells in vitro . Both drugs permitted the suppression of proliferation and IFN‐γ secretion by CD4 + CD25 − cells responding to allogeneic and other polyclonal stimuli; CTLA‐4 expression was abolished on CD4 + CD25 + cells without compromising their suppressive ability. Everolimus reduced IFN‐γ secretion by CD4 + CD25 − cells before the anti‐proliferative effect: this is a novel finding. Exogenous IL‐2 and IL‐15 could prevent the suppression of proliferation by CD4 + CD25 + cells and the drugs could not restore suppression. By contrast, suppression of IFN‐γ secretion was only slightly impeded with the exogenous cytokines. Finally, CD4 + CD25 + cells were more resistant than CD4 + CD25 − cells to the pro‐apoptotic action of the drugs. Together these data suggest that CD4 + CD25 + cells may still exert their effects in transplant patients taking immunosuppression that interferes with IL‐2 signaling.