Introduction Umbilical cord blood transplantation (CBT) has increas- ingly been performed as an alternative to human leuko- cyte antigen (HLA)-matched sibling or unrelated bone marrow transplantation (BMT).[1–3] Te advantages of CBT in comparison to BMT include rapid accessibility of cryopreserved cells, a less stringent HLA matching between donors and recipients, and a low risk of induc- ing severe graft-versus- host disease (GVHD).[4] On the other hand, cord blood contains a large population of immature unprimed highly functional regulatory T lymphocytes,[5, 6] that may actively and specifcally suppress unwanted allogeneic immune responses post- UCBT.[7, 8] Terefore, expansion or induction of Treg cells may be the most important reason for exploring therapeutic applications of UCB. Te IFN-λ gene family is comprised of three difer- ent genes: IFN-λ1 (IL-29), IFN-λ2 (IL-28A), and IFN-λ3 (IL-28B).[9, 10] IFN-λ2 is very similar to IFN-λ3 (96%), and IFN-λ1 exhibits 81% similarity with IFN-λ2.[11] Tey are expressed by human peripheral blood mononuclear cells and dendritic cells upon infection with viruses or stimulation with poly(I:C).[9, 10, 12] Even though nearly any cell type following viral infection can express IFN-λ, dendritic cells (DC) seem to be its most signifcant pro- ducers, specifcally plasmacytoid DC express high levels of IFN-λ following viral infection.[12] IFN-λs act through a cell surface receptor composed of two chains, the frst one (IFNLR1) being IFN-λ specifc and the second one (IL10R2) was shared among IL-10, IL-22 and IL-26.[9, 10, 13] Both receptor subunits are constitutively expressed in a wide variety of human cell lines and tissues,[9, 10] Immunopharmacology and Immunotoxicology, 2010; 32(2): 339–347 Address for Correspondence: Masoumeh Ebtekar, 1 Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, P.O. Box 14115 331, Tehran, Iran. E-mail: Ebtekarm@modares.ac.ir ORIGINAL ARTICLE Te efect of IL-28A on human cord blood CD4 + T cells Javad Arasteh 1 , Masoumeh Ebtekar 1 , Zahra Pourpak 2 , Ali Akbar Pourfatollah 1 , Zuhair Mohammad Hassan 1 , and Tahereh Farahmandian 3 1 Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran, 2 Immunology Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran, and 3 Valiasr Hospital, Tehran University of Medical Sciences, Tehran, Iran Abstract Background and aim: The utilization of umbilical cord blood transplantation (UCBT) has been increasing because of the potential advantage of rapid accessibility and the lesser risk of graft-versus-host disease (GVHD), thus allowing less strict HLA matching. IL-28A, also known as IFN-λ2, has been regarded as a member of a new cytokine family that shares some features with type I interferon (IFN) and was shown to have anti- viral activity. The aim of this study was to identify biological activity of IL-28 on cord blood CD4 + T cells. Materials and methods: In this study, we cultured CD4 + T cells with IL-28A (20 ng/ml), IL-2 (20 ng/ml) and 5μg/ml MACS Anti-Biotin MACSiBead Particles (bead-to-cell ratio 1:2) for 2 weeks. Results: Flow cytometry analyses showed that IL-28A cannot be efective on CD25 and Foxp3 expression on cord blood CD4 + T cells, and it is not involved in proliferation of these cells. Treg suppression assay also showed that this cytokine cannot induce production of regulatory T cells. Conclusion: We showed that IL-28A is not involved in expression of CD25 and Foxp3 markers and prolifera- tion of CD4 + CD25 − T cells, and that our fndings also suggest that induction of Foxp3 in T cells activated by anti-CD3/anti-CD28 does not result in the regulatory activity in these cells. Keywords: Interleukin 28A; CD4+ T cell; cord blood; regulatory T cells; Foxp3 (Received 01 July 2009; revised 17 August 2009; accepted 08 September 2009) ISSN 0892-3973 print/ISSN 1532-2513 online © 2010 Informa UK Ltd DOI: 10.3109/08923970903317445 http://www.informahealthcare.com/ipi