Induction of long-term survival of rat skin allografts by a novel, highly efficient anti-CD4 monoclonal antibody.

The new monoclonal antirat CD4 antibody RIB 5/2, which detects another epitope than those covered by W3/25 and MRC OX35, was tested for its immunosuppressive potency following skin allografting by using strain combinations with different genetic barriers in the MHC and genetic low- or high-responder background. High-dose and long-term therapy of the grafted rats led to a significant delay of the acute rejection (P < 0.01) in the strain combination Wistar Furth-to-BDX as well as in LEW1W-to-LEW1A. No significant prolongation of the mean allograft survival time was obtained for the high-responder rats (LEW1A-to-LEW1W). Cytofluorometric analysis revealed that RIB 5/2 exerts the immunosuppressive activity predominantly by modulation of the CD4 glycoprotein. Furthermore, the dependence of the humoral immune response against the mouse-globulins upon the administered protein quantity could be demonstrated.

The so-called interleukin-2 inhibitory activity of human serum is largely cytotoxic to mouse cells.

No specific interleukin-2 (IL-2) inhibitor has ever been demonstrated in human, mouse, or any other animal serum. Native mouse serum contains activities which completely inhibit IL-2-dependent and IL-2-independent in vitro proliferation of cells of different animal species by a non-cytotoxic mechanism. The decisive inhibitory component of mouse serum has a molecular weight of about 80,000, is heat-labile and has not been found in other animal sera. Also, native human serum completely suppresses the proliferation of various mouse cell types, predominantly by a cytotoxic effect caused by natural IgM antibodies and complement. Heat-inactivated human serum is no longer cytotoxic to mouse cells, and inhibits the proliferation of mouse cells much less than native serum. There is thus no evidence for a specific IL-2 inhibitor in mouse, human or other serum.

[Clinical value of interleukin 1- and interleukin 2-determinations in patients after kidney transplantation]. / Klinische Wertigkeit von Interleukin 1- und Interleukin 2-Bestimmungen bei Patienten nach Nierentransplantation.

In a retrospective study of allograft rejections in renal transplant recipients we examined the value of cytokine production monitoring. Interleukin 1 (IL 1) and interleukin 2 (IL 2) activities were determined in supernatants of mitogen-stimulated peripheral blood lymphocytes in 8 renal transplant recipients serially for a period up to 60 days after transplantation. LPS-induced IL 1 as well as PHA-induced IL 2 production in patients after renal transplantation were significantly decreased in comparison to healthy controls. Seven episodes of cellular rejection were diagnosed in renal allograft recipients during this time, only 4 rejection episodes, however, were associated with a rise in the IL 1 and simultaneous IL 2 production occurred for 2 up to 3 days before the diagnosis of rejection. Moreover there were 12 instances in which an elevation of IL 1 and IL 2 production was found independently from the rejection. In 8 cases the augmentation of IL 1 and IL 2 production could be associated with clinical infections. We conclude from these results that a cytokine monitoring for the diagnosis of allograft rejection does not seem to be useful.