Effects of CD25 monoclonal antibody on proliferative and effector functions of alloactivated human T cells in vitro.
Prophylactic treatment with CD25 mAb has led to a significant decrease of acute rejection rates after renal transplantation. However, despite its inhibitory effect on T cell proliferation and effector functions, rejections still occur. To obtain more insight in persistent alloreactivity, we evaluated the effects of the chimeric IgG1kappa CD25 mAb Basiliximab on proliferation and differentiation of alloactivated T cells from healthy individuals in vitro. Moreover, the capacity of other members of the common cytokine-receptor gamma-chain family to overcome the inhibitory effects of CD25 mAb was studied. The CD25 mAb appeared to limit expansion of alloreactive lymphocytes rather than blocking entry into cell cycle, and it did so irrespective of the previous antigen experience of the cells. Both CD4+ and CD8+ alloresponsive lymphocytes showed diminished intracellular expression of IFN-gamma, TNF-alpha, perforin and granzyme B. Remarkably, cytotoxicity was completely abolished. IL-7, IL-15 and IL-21 could bypass the inhibitory effects of the CD25 mAb on both proliferation and cytotoxicity. In conclusion, persistent alloreactivity in the presence of therapeutic concentrations of CD25 mAb may be caused by alloreactive T cells that still produce cytokines that can damage the allograft. In addition, other members of the common cytokine-receptor gamma-chain family can rescue the proliferative and cytotoxic activity of these alloreactive T cells.
Rowshani
Ajda T
AT
Division of Clinical Immunology and Rheumatology, Academic Medical Center, Amsterdam, The Netherlands.
Uss
Alena
A
Division of Clinical Immunology and Rheumatology, Academic Medical Center, Amsterdam, The Netherlands.|Laboratory for Experimental Immunology, Academic Medical Center, Amsterdam, The Netherlands.
Yong
Si-La
SL
Division of Clinical Immunology and Rheumatology, Academic Medical Center, Amsterdam, The Netherlands.
van Lier
René A W
RAW
Laboratory for Experimental Immunology, Academic Medical Center, Amsterdam, The Netherlands.
Ten Berge
Ineke J M
IJM
Division of Clinical Immunology and Rheumatology, Academic Medical Center, Amsterdam, The Netherlands.|Renal Transplant Unit, Department of Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands.
D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000077552:Basiliximab; D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003601:Cytotoxicity Tests, Immunologic; D006801:Humans; D007378:Interleukins / Q000494:pharmacology; D007519:Isoantigens / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D011993:Recombinant Fusion Proteins; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology
D000911:Antibodies, Monoclonal; D016207:Cytokines; D007378:Interleukins; D007519:Isoantigens; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins; D000077552:Basiliximab