THE DEVELOPMENT OF NATURAL-KILLER (NK) CELLS FROM THY-1(LO)LIN(-)SCA-1(+) STEM-CELLS - ACQUISITION BY NK CELLS IN-VIVO OF THE HOMING RECEPTOR MEL-14 AND THE INTEGRIN MAC-1

The present study aimed to follow the development of natural killer (NK) cells in lethally irradiated BA mice reconstituted with 500 syngeneic Thy 1.1(lo)Lin(-)Sca-1(+) stem cells. The proportions of NK 1.1(+) lymphoid cells were assessed from smears of cell suspensions from the spleen and bone marrow by means of immunofluorescence microscopy, at 7, 9, 11, 14, 17, 21, 24 and 28 days after stem cell injection. At the same intervals, moreover, the proportions of NK 1.1(+) lymphoid cells bearing either the homing receptor recognized by mAb MEL-14, or the integrin Mac-1 were recorded using double immunofluorescence microscopy, labelling variously with fluorescein isothiocynate and avidin I Texas Red, The results demonstrate that NK 1.1(+) lymphoid cells re-appear by 11 (spleen) to 14 (bone marrow) days after injecting syngeneic Thy 1.1(lo)Lin(-)Sca-1(+) stem cells. Moreover, in the absence of apparent stimulation, the newly developed NK 1.1(+) lymphoid cells spontaneously express the homing receptor MEL-14 and the integrin Mac-1. The very similar patterns of acquisition of these latter 2 molecules on NK 1.1(+) cells in the spleen during their recovery in the post-stem cell injection period suggests that MEL-14 and Mac-1 may co-express on the same NK 1.1(+) cells. The absence, or low levels of both molecules on the newly developed NK 1.1(+) cells while still in the bone marrow suggests that NK cells may progressively acquire these molecules outside that organ, en route to and/or within the vasculature of the spleen, their normal, primary destiny.