During the first postoperative months, exposure to MPA is low in a considerable proportion of liver transplant patients receiving MMF at a fixed dose of 1 g bid. MPA monitoring appears necessary in these patients.
Background: Graft survival depends on adequate immunosuppression. To evaluate the effect on the immune system of immunosuppressive therapies using calcineurin inhibitors (CNIs), several pharmacodynamic indices have been proposed to complement pharmacokinetic data. In this preliminary study we compared some of these parameters during combined immunosuppressant therapies. Methods: We treated 65 stable renal transplant recipients with cyclosporin A (CsA; n ؍ 16), tacrolimus (TRL; n ؍ 10); CsA ؉ mycophenolate mofetil (MMF; n ؍ 14); TRL ؉ MMF (n ؍ 13), and MMF (n ؍ 12). Twelve nontreated healthy controls were also included. Calcineurin activity (CNA) in peripheral blood mononuclear cells was measured using 32 P-labeled peptide. Interleukin-2 (IL-2) and interferon-␥ production in phytohemagglutinin-activated whole blood were measured at 0 and 2 h postdose. The areas under the curves, c min , c max , and concentration at 2 h (c 2 h ) were also measured.
The induction of T cell mitogenesis through CD3 is a complex process that requires at least two signals. The first one can be provided by Sepharose-bound CD3. The second one is normally provided by monocytes. The signal provided by Sepharose-bound CD3 is unable by itself to induce mitogenesis in monocyte highly depleted cells (MHDC). We describe here that the monoclonal antibody (mAb) 72-5D3 belonging to CD45 (T200), which was not mitogenic by itself, could replace monocytes when MHDC were activated by Sepharose-bound CD3. That is to say, in the absence of monocytes, mAb 72-5D3 gave a second signal necessary for T cell proliferation. Using eleven anti-CD45 mAb from other investigators we show that this effect is not a peculiar characteristic of 72-5D3 mAb. The effect of the mAb 72-5D3 was only effective in CD4-positive cells and was not observed when MHDC were activated with either soluble CD3 or concanavalin A. As both phorbol myristate acetate and mAb 72-5D3 can replace monocytes, a comparative study of their effects was undertaken. Phorbol myristate acetate but not mAb 72-5D3 induced proliferation of MHDC when recombinant interleukin 2 (rIL2) was added. On the other hand mAb 72-5D3 induced IL2 production in MHDC activated by Sepharose-bound CD3 and increased the IL2 production in Sepharose-bound CD3-activated peripheral blood mononuclear cells. In conclusion, data presented in this report indicate that the T200 molecule could be involved in T cell proliferation by giving a signal that induces the production of IL2 and bypasses the necessity of monocytes.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.