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

• Published in: Cancer Immunology, Immunotherapy Immunotherapy, 2013-01, Vol.62 (1), p.113-124
• Main Authors: Borge, Mercedes, Nannini, Paula Romina, Morande, Pablo Elías, Jancic, Carolina, Bistmans, Alicia, Bezares, Raimundo Fernando, Giordano, Mirta, Gamberale, Romina
• Format: Article
• Language: English
• Subjects: Antigens, CD - biosynthesis; Cancer Research; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD4-Positive T-Lymphocytes - pathology; Cell Proliferation; Cell Separation; Chemokine CXCL12 - immunology; Chemokine CXCL12 - metabolism; Flow Cytometry; Humans; Immunology; Immunophenotyping; Leukemia, Lymphocytic, Chronic, B-Cell - immunology; Leukemia, Lymphocytic, Chronic, B-Cell - metabolism; Lymphocyte Activation - immunology; Medicine; Medicine & Public Health; Microscopy, Confocal; Oncology; Original; Original Article
• ISSN: 0340-7004; 1432-0851
• DOI: 10.1007/s00262-012-1320-7

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.