title: CXCL12 is a costimulator for CD4+ T cell activation and proliferation in chronic lymphocytic leukemia patients.
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.
authors: Laboratorio de Inmunología Oncológica, Instituto de Medicina Experimental (IMEX) - CONICET, Academia Nacional de Medicina, Pacheco de Melo 3081 (1425), Ciudad de Buenos Aires, Argentina.
authors: Mercedes
authors: M
authors: Borge
authors: Paula Romina
authors: PR
authors: Nannini
authors: Pablo Elías
authors: PE
authors: Morande
authors: Carolina
authors: C
authors: Jancic
authors: Alicia
authors: A
authors: Bistmans
authors: Raimundo Fernando
authors: RF
authors: Bezares
authors: Mirta
authors: M
authors: Giordano
authors: Romina
authors: R
authors: Gamberale
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D002469:Cell Separation; D054377:Chemokine CXCL12 / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D018613:Microscopy, Confocal
chemical_list: D015703:Antigens, CD; D054377:Chemokine CXCL12