INVESTIGADORES
GAMBERALE Romina
congresos y reuniones científicas
Título:
CXCL12 is a costimulator for CD4+ T cell activation and proliferation in Chronic Lymphocytic Leukemia (CLL) patients
Autor/es:
BORGE MERCEDES; NANNINI PAULA ROMINA; MORANDE PABLO; JANCIC CAROLINA; ZANETTI SAMANTA ROMINA; BISTMANS ALICIA; BEZARES RAIMUNDO FERNANDO; GIORDANO MIRTA; GAMBERALE ROMINA
Lugar:
Houston
Reunión:
Encuentro; V Young CLL Investigators´Meeting; 2011
Resumen:
B cell chronic lymphocytic
leukemia (CLL) cells proliferate in lymphoid tissues in close contact with
activated T cells, stromal cells and accessory myeloid cells, such as nurse-like
cells (NLC) which favor CLL cell survival and proliferation. CXCL12 is a highly conserved
chemokine produced by stromal cells and NLC and CXCR4, its main receptor, was
shown to induce CLL and T cell migration and leukemic cell activation and
survival. The aim of this study was to determine whether CXCL12 may enhance the
activation and proliferation of T cells from CLL patients. Thus, PBMC or purified
T cells from CLL patients were cultured for 2 hours with or without recombinant
human CXCL12 (rhCXCL12), then transferred to cell culture plates coated with immobilized anti-CD3 mAb and after 24hs of
culture, the expression of the activation markers CD25, CD69 and CD154 on CD4+
T cells was evaluated by FACS. We found that the combination of anti-CD3 and rhCXCL12
significantly increased the expression of all activation markers beyond the one
induced by anti-CD3 alone (p<0.01, n=18). No significant differences were
observed when samples were segregated according to ZAP-70 or CD38 expression.
Moreover, we found that rhCXL12 enhances IFNγ production (p<0.01, n=18) and
proliferation (p<0.01, n=10) of activated CD4+ T cells from CLL
patients. More interestingly, leukemic cell activation (p<0.05, n=10) and
proliferation (p<0.05, n=10) was enhanced by activated T cells in the presence
of rhCXCL12. In addition, autologous NLC increased the activation (p<0.01,
n=10) and proliferation (p<0.05, n=5) of CD4+ T cells from CLL
patients partially through a CXCR4-dependent mechanism. Altogether, our results
prompted us to hypothesize that CXCL2 production by lymphoid tissue microenvironment in CLL patients
may play a key dual role for T cell physiology, functioning not only as a
chemoattractant but also as a costimulatory factor for activated T cells.