OBJECTIVE: CpG-oligodeoxynucleotides (CpG-ODN) have been shown to induce proliferation, cytokine production, and surface molecule regulation in normal and malignant human B cells. In the present study, we investigated the potential of CpG-ODN to induce functional high-affinity receptors in leukemic and normal B cells and the effects of costimulation with IL-2 on proliferation, cytokine secretion, and surface molecule regulation. METHODS: Highly purified B cells from B-CLL patients and normal controls were stimulated with CpG-ODN with or without IL-2. Expression of CD25 was determined using FACS, and the presence of high-affinity IL-2 receptors was determined by scatchard analysis. Costimulatory effects of IL-2 and CpG-ODN were investigated using proliferation assays, ELISA (IL-6, TNF-alpha), and FACS analysis (CD80, CD86 expression). Reactivity of autologous and allogeneic T cells toward activated B-CLL cells was determined in mixed lymphocyte reactions and Interferon-gamma Elispot assays. RESULTS: The CpG-ODN DSP30 caused a significantly stronger induction of the IL-2 receptor alpha chain in malignant as compared with normal B cells (p = 0.03). This resulted in the expression of functional high-affinity IL-2 receptors in B-CLL cells, but fewer numbers of receptors with less affinity were expressed in normal B cells. Although addition of IL-2 to CpG-ODN-stimulated cells augmented proliferation in both normal B cells and B-CLL cells, no costimulatory effect on cytokine production or surface molecule expression could be observed in normal B cells. In contrast, TNF-alpha and IL-6 production was increased in B-CLL cells, and the expression of CD80 and CD86 was further enhanced when IL-2 was used as a costimulus. Autologous and allogeneic immune recognition of B-CLL cells stimulated with CpG-ODN and IL-2 was increased compared with B-CLL cells stimulated with CpG-ODN alone. CONCLUSION: Stimulation of B-CLL cells with CpG-ODN and IL-2 might be an attractive strategy for potential immunotherapies for B-CLL patients.
OBJECTIVE: CpG-oligodeoxynucleotides (CpG-ODN) have been shown to induce proliferation, cytokine production, and surface molecule regulation in normal and malignant human B cells. In the present study, we investigated the potential of CpG-ODN to induce functional high-affinity receptors in leukemic and normal B cells and the effects of costimulation with IL-2 on proliferation, cytokine secretion, and surface molecule regulation. METHODS: Highly purified B cells from B-CLL patients and normal controls were stimulated with CpG-ODN with or without IL-2. Expression of CD25 was determined using FACS, and the presence of high-affinity IL-2 receptors was determined by scatchard analysis. Costimulatory effects of IL-2 and CpG-ODN were investigated using proliferation assays, ELISA (IL-6, TNF-alpha), and FACS analysis (CD80, CD86 expression). Reactivity of autologous and allogeneic T cells toward activated B-CLL cells was determined in mixed lymphocyte reactions and Interferon-gamma Elispot assays. RESULTS: The CpG-ODN DSP30 caused a significantly stronger induction of the IL-2 receptor alpha chain in malignant as compared with normal B cells (p = 0.03). This resulted in the expression of functional high-affinity IL-2 receptors in B-CLL cells, but fewer numbers of receptors with less affinity were expressed in normal B cells. Although addition of IL-2 to CpG-ODN-stimulated cells augmented proliferation in both normal B cells and B-CLL cells, no costimulatory effect on cytokine production or surface molecule expression could be observed in normal B cells. In contrast, TNF-alpha and IL-6 production was increased in B-CLL cells, and the expression of CD80 and CD86 was further enhanced when IL-2 was used as a costimulus. Autologous and allogeneic immune recognition of B-CLL cells stimulated with CpG-ODN and IL-2 was increased compared with B-CLL cells stimulated with CpG-ODN alone. CONCLUSION: Stimulation of B-CLL cells with CpG-ODN and IL-2 might be an attractive strategy for potential immunotherapies for B-CLL patients.
Authors: Natarajan Muthusamy; Heather Breidenbach; Leslie Andritsos; Joseph Flynn; Jeffrey Jones; Asha Ramanunni; Xiaokui Mo; David Jarjoura; John C Byrd; Nyla A Heerema Journal: Cancer Genet Date: 2011-02
Authors: Zhao Xiaoxia; Ni Weihua; Zhang Qingyong; Wang Fengli; Li Yingying; Sun Xiaxia; Liu Zhonghui; Tai Guixiang Journal: Clin Transl Oncol Date: 2011-07 Impact factor: 3.405
Authors: Bernd Jahrsdörfer; Sue E Blackwell; James E Wooldridge; Jian Huang; Melinda W Andreski; Laura S Jacobus; Christiana M Taylor; George J Weiner Journal: Blood Date: 2006-06-29 Impact factor: 22.113
Authors: Rashmi Gupta; Xiao J Yan; Jacqueline Barrientos; Jonathan E Kolitz; Steven L Allen; Kanti Rai; Nicholas Chiorazzi; Patricia K A Mongini Journal: J Immunol Date: 2018-08-01 Impact factor: 5.422
Authors: F Pozzo; T Bittolo; E Vendramini; R Bomben; P Bulian; F M Rossi; A Zucchetto; E Tissino; M Degan; G D'Arena; F Di Raimondo; F Zaja; G Pozzato; D Rossi; G Gaidano; G Del Poeta; V Gattei; M Dal Bo Journal: Leukemia Date: 2017-03-21 Impact factor: 11.528
Authors: Leslie A Andritsos; Amy J Johnson; Gerard Lozanski; William Blum; Cheryl Kefauver; Farrukh Awan; Lisa L Smith; Rosa Lapalombella; Sarah E May; Chelsey A Raymond; Da-Sheng Wang; Robert D Knight; Amy S Ruppert; Amy Lehman; David Jarjoura; Ching-Shih Chen; John C Byrd Journal: J Clin Oncol Date: 2008-04-21 Impact factor: 44.544