11. B cell chronic lymphocytic leukemia (CLL): CXCL12 and nurse like cells (NLCs) enhance the activation of T cells from high-risk or low-risk patients.

BORGE MERCEDES; NANNINI PAULA ROMINA; MORANDE PABLO; ZANETTI SAMANTA ROMINA; BEZARES RAIMUNDO FERNANDO; SANCHEZ AVALOS JULIO; GIORDANO MIRTA; GAMBERALE ROMINA

caba

Congreso; 1° French-Argentine Immunology Congress,; 2010

  Leukemic B cells from CLL patients proliferate in lymphoid organs where activated T cells and CXCL12 producers` stromal cells and/or NLCs provide them survival and proliferative signals. Patients with poor prognosis, who develop an aggressive disease, usually express the prognostic markers ZAP70 and CD38 in their leukemic cells. The absence of these molecules is mostly found in leukemic cells from good prognosis patients, who exhibit an indolent disease. We have previously described that CXCL12 can increase (co-stimulate) the expression of CD40L, CD25 and CD69 on activated T cells from CLL patients, and that T cells from good prognosis patients have a lower migratory response to these chemokine than T cells from poor prognosis patients. The aims of these study were: a) to determinate if CXCL12 could increase the expression of IFNγ and proliferation of activated T cells from CLL patients; b) to compare the co-stimulation induced by CXCL12 on activated T cells from CLL patients with good and poor prognosis; c) to study if NLCs could induce a CXCL12´s mediated co-stimulation on activated T cells from CLL patients. We activated PBMC of CLL patients with (or without) anti-CD3 mAb in the presence (or absence) of CXCL12 (n=10) and found a higher expression of IFNγ (p=0,01) and proliferation (p=0,004) of activated T cells in the presence of CXCL12 than in the absence of it. We found no differences in the co-stimulation induced by CXCL12 on activated T cells from CLL patients of good and poor prognosis segregated by ZAP70 or CD38 (p> 0,05). Then, we activated PBMC of CLL patients in the presence (or absence) of NLCs (n=6), and found a higher expression of CD25 and CD69 on activated T cells in the presence of NLCs than in the absence of these cells (p= 0,01, p=0,03), that was no longer significant when the CXCL12`s receptor was blocked on T cells (p> 0,05).   CXCL12`s producers NLCs and activated T cells are found on lymphoid organs of CLL patients were the proliferation of the leukemic clone occurs. We propose that within the lymphoid organs of CLL patients, CXCL12 could be increasing proliferative and survival signals to CLL cells given by T cells, such as CD40L and IFNγ, contributing to disease progression regardless of the patient`s prognosis.