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Pre-Clinical Studies

Effect of interleukin-15 on effector and regulatory function of anti-CD3/anti-CD28-stimulated CD4+ T cells

Bone Marrow Transplantation volume 37, pages 881–887 (2006)Cite this article

Abstract

Autologous transfer of anti-CD3/anti-CD28 (CD3/CD28)-activated CD4+ T cells may benefit patients receiving autologous stem cell transplant with severe CD4 lymphopenia. Interleukin (IL)-15, an IL-2-like cytokine that promotes T cell survival may enhance immune reconstitution in conjunction with adoptive immunotherapy. We investigated the effect of IL-15 on effector and regulatory function of CD3/CD28-activated CD4+ T cells. IL-15 upregulated CD45RO and CD25 whereas it downregulated CD62L expression of CD3/CD28-stimulated CD4+ T cells. Both type 1 (IFN-γ, tumor necrosis factor (TNF)-α) and type 2 (IL-5 and IL-10) production by CD3/CD28-activated CD4+ T cells was further enhanced by IL-15. Co-culture experiments revealed that CD3/CD28-activated CD4+ T cells downregulated proliferation of autologous peripheral blood lymphocytes (PBLs) and CD8+ PBL subsets upon TCR ligation, a contact-dependent effect that was further enhanced by pretreatment with IL-15. Flow cytometric analysis of cell mixture with carboxyfluorescein diacetate succinimidyl ester and Annexin-V-PE staining revealed that CD3/CD28+IL-15-activated CD4+ T cells showed increased apoptosis over CD4+ T cells stimulated with CD3/CD28 alone. Taken together, pretreatment of CD3/CD28-activated CD4+ T cells with IL-15 may increase regulatory function but may aggravate activation-induced apoptosis of CD3/CD28 CD4+ T cells.

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Acknowledgements

This study was supported by grants from the National Science Council of Republic of China (grant number NSC93-2314-B-182A-073 and NSC94-2314-B-182A-095) and a grant from the Chang-Gung Memorial Hospital (grant number CMRPG 32024).

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Authors and Affiliations

  1. Division of Asthma, Department of Pediatrics, Allergy and Rheumatology, Chang Gung Children's Hospital, Chang Gung University, Taoyuan, Taiwan

    S-J Lin

  2. Department of Obstetrics/Gynecology, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan

    P-J Cheng

  3. Department of Microbiology and Immunology, Graduate Institute of Basic Medical Science, Chang Gung University, Taoyuan, Taiwan

    S-S Hsiao

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  1. S-J Lin
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  3. S-S Hsiao
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Correspondence to S-J Lin.

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Lin, SJ., Cheng, PJ. & Hsiao, SS. Effect of interleukin-15 on effector and regulatory function of anti-CD3/anti-CD28-stimulated CD4+ T cells. Bone Marrow Transplant 37, 881–887 (2006). https://doi.org/10.1038/sj.bmt.1705348

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