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

被引:0
作者
S-J Lin
P-J Cheng
S-S Hsiao
机构
[1] Allergy and Rheumatology,Division of Asthma, Department of Pediatrics
[2] Chang Gung Children's Hospital,Department of Obstetrics/Gynecology
[3] Chang Gung University,Department of Microbiology and Immunology
[4] Chang Gung Memorial Hospital,undefined
[5] Chang Gung University,undefined
[6] Graduate Institute of Basic Medical Science,undefined
[7] Chang Gung University,undefined
来源
Bone Marrow Transplantation | 2006年 / 37卷
关键词
anti-CD3/anti-CD28; CD4; T cells; interleukin-15;
D O I
暂无
中图分类号
学科分类号
摘要
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.
引用
收藏
页码:881 / 887
页数:6
相关论文
共 165 条
  • [1] Weinberg K(1995)The effect of thymic function on immunocompetence following bone marrow transplantation Biol Blood Marrow Transplant 1 18-23
  • [2] Annett G(2000)Prolonged CD4 depletion after sequential autologous peripheral blood progenitor cell infusions in children and young adults Blood 96 754-762
  • [3] Kashyap A(1998)Immune reconstitution and immunotherapy after autologous hematopoietic stem cell transplantation Blood 92 1471-1490
  • [4] Lenarsky C(2004)Optimization of human T-cell expansion J Immunother 27 405-418
  • [5] Forman SJ(2003) using magnetic beads conjugated with anti-CD3 and anti-CD28 antibodies Blood 102 2004-2013
  • [6] Parkman R(2004)Adoptive transfer of costimulated T cells induces lymphocytosis in patients with relapsed/refractory non-Hodgkin's lymphoma following CD34-selected hematopoietic cell transplantation Bone Marrow Transplant 33 53-60
  • [7] Mackall CL(2004)Molecular remission of CML after autotransplantation followed by adoptive transfer of costimulated autologous T cells Clin Immunol 111 262-274
  • [8] Stein D(2004)Immune reconstitution following autologous transfers of CD3/CD28 stimulated CD4(+) T cells to HIV-infected persons Curr Opin Oncol 16 542-546
  • [9] Fleisher TA(2005)A review of recent findings involving interleukin-2-based cancer therapy J Antimicrob Chemother 55 401-409
  • [10] Brown MR(2001)Partial immune reconstitution following highly active antiretroviral therapy: can adjuvant interleukin-2 fill the gap? Blood 97 14-32