Selective in vivo deletion of alloactivated TH1 cells by OKT3 monoclonal antibody in acute rejection.
The OKT3 monoclonal antibody (mAb) recognizing the CD3 complex on human T-cells has been shown to be an effective immunosuppressive agent for the treatment and the prevention of acute rejection episodes in allograft recipients [1]. Following the initial doses of OKT3 mAb, activation of T lymphocytes and monocytes is observed. This is accompanied by a massive cytokine release, particularly following the first injection. The mAb opsonizes the circulating T-cells and the coated cells disappear quickly from circulation. OKT3 mAb is commonly administered for 5-10 days. The manifestation of side effects weeks (cytomegalovirus infection/disease, bacterial and fungal infections) or even months (Epstein-Barr-Virus related lymphoproliferative disease) after therapy as well as the good long-term effects on graft function suggest long-lasting immunosuppressive effects. Since peripheral T-cells reappear in the circulation already during therapy (with modulated CD3/T-cell receptor complex) and T-cell counts reach commonly pretreatment levels within 2-3 days after cessation of OKT3 mAb, the long-lasting immunosuppressive effects are not simply explainable by T-cell depletion. We wondered whether T-cells reappearing in the circulation after cessation of therapy, were functionally different from those before OKT3 mAb therapy. Our data suggest a selective depletion of activated T-cells particularly of type 1-like T-cells by OKT3 mAb resulting in long-lasting immune deviation that may explain the long-term effects of OKT3 mAb treatment.
Reinke
P
P
Department of Nephrology and Intensive Care, Virchow Clinic, Humboldt-University, Berlin, Germany.
Schwinzer
H
H
Höflich
C
C
Ode-Hakim
C
C
Döcke
W D
WD
Frei
U
U
Volk
H D
HD
D017637:Clonal Deletion; D006084:Graft Rejection / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D016030:Kidney Transplantation / Q000276:immunology*; D016853:Muromonab-CD3 / Q000494:pharmacology*; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000096:biosynthesis; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D007166:Immunosuppressive Agents; D016853:Muromonab-CD3; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma