Cancer Immunology, Immunotherapy

, Volume 62, Issue 1, pp 113–124

CXCL12 is a costimulator for CD4+ T cell activation and proliferation in chronic lymphocytic leukemia patients

  • Mercedes Borge
  • Paula Romina Nannini
  • Pablo Elías Morande
  • Carolina Jancic
  • Alicia Bistmans
  • Raimundo Fernando Bezares
  • Mirta Giordano
  • Romina Gamberale
Original article

Abstract

Activated T cells from patients with chronic lymphocytic leukemia (CLL) provide survival and proliferative signals to the leukemic clone within lymphoid tissues. Recruitment of both, CLL cells and T lymphocytes, to this supportive microenvironment greatly depends on CXCL12 production by stromal and myeloid cells. CXCL12 also supplies survival stimuli to leukemic B cells, but whether it exerts stimulatory effects on T lymphocytes from CLL patients is unknown. In order to evaluate the capacity of CXCL12 to increase CD4+ T cell activation and proliferation in CLL patients, peripheral blood mononuclear cells were cultured with or without recombinant human CXCL12 or autologous nurse-like cells, and then T cell activation was induced by anti-CD3 mAb. CXCL12 increases the proliferation and the expression of CD25, CD69, CD154, and IFNγ on CD3-stimulated CD4+ T cells from CLL patients, similarly in T cells from ZAP-70+ to ZAP-70 patients. Autologous nurse-like cells establish a close contact with CD4+ T cells and increase their activation and proliferation partially through a CXCR4-dependent mechanism. In addition, we found that activated T cells in the presence of CXCL12 enhance the activation and proliferation of the leukemic clone. In conclusion, CXCL12 production by lymphoid tissue microenvironment in CLL patients might play a key dual role on T cell physiology, functioning not only as a chemoattractant but also as a costimulatory factor for activated T cells.

Keywords

Chronic lymphocytic leukemia T cell activation CXCL12 Nurse-like cells 

Supplementary material

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Mercedes Borge
    • 1
    • 4
  • Paula Romina Nannini
    • 1
    • 4
  • Pablo Elías Morande
    • 1
    • 4
  • Carolina Jancic
    • 1
    • 4
  • Alicia Bistmans
    • 2
  • Raimundo Fernando Bezares
    • 3
  • Mirta Giordano
    • 1
    • 4
  • Romina Gamberale
    • 1
    • 4
  1. 1.Laboratorio de Inmunología Oncológica, Instituto de Medicina Experimental (IMEX) - CONICETAcademia Nacional de MedicinaCiudad de Buenos AiresArgentina
  2. 2.Hospital J. M. Ramos MejíaCiudad de Buenos AiresArgentina
  3. 3.Hospital General de Agudos Dr. T. ÁlvarezCiudad de Buenos AiresArgentina
  4. 4.Departamento de Microbiología Parasitología e Inmunología, Facultad de MedicinaUniversidad de Buenos AiresCiudad de Buenos AiresArgentina

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