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*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

16 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)113-124
Number of pages12
JournalCancer Immunology, Immunotherapy
Issue number1
Publication statusPublished - Jan 2013
Externally publishedYes


  • CXCL12
  • Chronic lymphocytic leukemia
  • Nurse-like cells
  • T cell activation


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