- 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 M; NANNINI P; MORANDE P; ZANETTI S; GALLETTI J; BEZARES RF; SÁNCHEZ AVALOS JC; GIORDANO M; GAMBERALE R

Congreso; First French-Argentine Immunology Congress; 2010

The clinical course of CLL is very heterogeneous, with patients who develop an aggressive disease that lead to an early death (high-risk group) and others who survive for decades (low-risk group). Activated T cells from CLL patients provide survival and proliferative signals to the leukemic clone within lymphoid organs. We have previously reported that T cells from low-risk CLL patients show a lower migratory capacity towards CXCL12 (a chemokine produced in lymphoid organs by stromal cells or NLCs) compared to T cells from high-risk patients. Given that CXCL12 also exerts a co-stimulatory activity on T cells, we asked whether this capacity could be impaired in T cells from low-risk compared to high-risk patients favoring the indolent course of the disease in the former group. The aims of this study were: a) to evaluate if CXCL12 increases the proliferation and production of the anti-apoptotic cytokine IFNγ by activated T cells from CLL patients; b) to compare the effects of CXCL12 on T cells from high-risk and low-risk groups and c) to study if NLCs can also enhance the activation of T cells. When we cultured T cells from CLL patients (n=10) with and without anti-CD3 we found a higher proliferation (p=0.004) and expression of IFNγ (p=0.01) if T cells were activated in the presence of CXCL12. We observed a similar co-stimulation induced by CXCL12 on T cells from both CLL risk groups (p>0.05). Finally, we found higher expression of CD25 (p=0.01) and CD69 (p=0.03) when activated T cells were cultured in the presence of autologous NLCs (n=6). Preliminary blocking experiments showed that CXCL12 production by NLC may account for the T cell co-stimulation observed (n=3). Our results suggest that the presence of CXCL12 in lymphoid organs may enhance the activation of T cells. Because no differences were found in the co-stimulation induced by CXCL12 in T cells from both groups of CLL patients, other processes, such as the lower migratory response of low-risk T CLL cells might favor the indolent clinical course of the disease in these patients.