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Molecular Medicine

, Volume 10, Issue 7–12, pp 96–103 | Cite as

Dendritic Cells from Chronic Lymphocytic Leukemia Patients Are Normal Regardless of Ig V Gene Mutation Status

  • Davorka Messmer
  • Gloria Telusma
  • Tarun Wasil
  • Bradley T Messmer
  • Steven Allen
  • Kanti R Rai
  • Nicholas Chiorazzi
Articles

Abstract

Patients with B-type chronic lymphocytic leukemia (B-CLL) segregate into 2 subgroups based on the mutational status of the immunoglobulin (Ig) V genes and the patients in these subgroups follow very different clinical courses. To examine whether dendritic cells (DCs) generated from CLL patients can be candidates for immune therapy, we compared the phenotypic and functional capacities of DCs generated from patients of the 2 CLL subgroups (normal age-matched subjects [normal-DCs]). Our data show that immature DCs from B-CLL patients (B-CLL-DCs) have the same capacity to take up antigen as those from normal controls. Furthermore, B-CLL-DCs generated from the 2 CLL subgroups up-regulated MHC-II, CD80, CD86, CD83, CD40, and CD54 and down-regulated CD206 in response to stimulation with a cocktail of cytokines (CyC) and secreted increased levels of tumor necrosis factor α, interleukin (IL)-8, IL-6, IL-12 (p70), and RANTES in a manner typical of mature normal-DCs. Interestingly, CD54 was significantly more up-regulated by CyC in B-CLL-DCs compared with normal-DCs. Except for CD54, no significant differences in surface molecule expression were observed between normal-DCs and B-CLL-DCs. B-CLL-DCs from both subgroups, including 6 patients with VH1-69, that usually fare poorly, presented tetanus toxoid to autologous T cells in vitro similar to normal-DCs. Our data show that DCs generated from the B-CLL subgroup with unmutated Ig V genes are functionally normal. These results are very promising for the use of DCs from patients with poor prognosis for immunotherapy.

Notes

Acknowledgments

We especially wish to thank Ann Way for organizing patient blood draws and tetanus toxoid vaccination. We thank Catherine Rapelje for FACS analyses and Emilia Albesiano, Scott Orenstein, and past members of the lab for IgV sequence analyses. These studies were supported in part by General Clinical Research Center Grant (M01 RR018535) from the National Center for Research Resources, the Jean Walton Fund for Lymphoma & Myeloma Research (to NC), and the Laurie Strauss Leukemia Foundation (to DM).

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Copyright information

© Feinstein Institute for Medical Research 2004

Authors and Affiliations

  • Davorka Messmer
    • 1
    • 2
  • Gloria Telusma
    • 1
  • Tarun Wasil
    • 3
  • Bradley T Messmer
    • 1
  • Steven Allen
    • 2
  • Kanti R Rai
    • 3
  • Nicholas Chiorazzi
    • 1
    • 2
  1. 1.The Laboratory of Experimental Immunology, Institute for Medical ResearchNorth Shore-LIJ Health SystemManhassetUSA
  2. 2.Departments of MedicineNorth Shore University Hospital and NYU School of MedicineManhassetUSA
  3. 3.Departments of MedicineLong Island Jewish Medical Center and Albert Einstein College of MedicineNew Hyde ParkUSA

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