NK cells in chronic lymphocytic leukemia (CLL): defetive expression of CD62L and interferon gamma (IFN-gamma) production

ZANETTI, SAMANTA; MORANDE, PABLO; BORGE, MERCEDES; NANNINI, PAULA; BEZARES, FRANCISCO; ZWIRNER, NORBERTO WALTER; GAMBERALE, ROMINA; GIORDANO, MIRTA NILDA

Buenos Aires

Congreso; 1º Congreso Franco-Argentino de Inmunología y 58a Reunión Anual de la Sociedad Argentina de Inmunología; 2010

Sociedad Argentina de Inmunología y Sociedad Francesa de Inmunología

Patients with CLL exhibit a progressive deficiency in the immune response which has been associated to autoimmune disorders, recurrent infections and second malignancies. Given the key role of NK cells in immunesurveillance, we have evaluated the expression of CD62L and CCR7, two molecules involved in NK migration to secondary lymphoid tissues in CD56+CD3- cells from CLL patients and healthy age-matched donors. By flow cytometric analysis we observed a lower proportion of CD62L+ cells in peripheral blood NK cells from CLL patients (30.4 ± 1.6) compared to healthy donors 44.8 ± 2.6 (results are expressed as the mean ± SD, n= 28 and 45 respectively, p<0.01). In regard to NK cells expressing CCR7, we found a comparable low proportion of positive cells in both groups (6.8 ± 3.4 versus 7.4 ± 2.4, healthy donors vs CLL patients, n= 11 and 9 respectively, not significant), except for three CLL patients who had more than 40% of CD56+CD3-CCR7+ cells. We also analyzed the functional activity of NK cells from CLL patients by evaluating their capacity to produce IFNγ when activated with Poly I:C, a TLR-3 specific agonist. To this aim, we incubated peripheral blood mononuclear cells for 24 h in the presence of poly I:C (50 ug/ml) and determined the proportion of NK that produced IFNγ by flow cytometry. There was no difference in spontaneous IFNγ production between NK cells from healthy donors and CLL patients (% CD56+CD3-INFγ+ cells 1.8 ± 0.3 vs 1.7 ± 0.4, n=17 and 19 respectively). By contrast, NK cells from CLL patients showed an impaired response to poly I:C stimulation (% CD56+CD3-INFγ+ cells 17.0 ± 2.8 vs 9.5 ± 2.5, p<0.01). In conclusion, our findings indicate that NK cells from CLL patients present phenotypic and functional defects that may be implicated in the high incidence of second malignancies in this pathology.