Kinetics of interleukin-2 induced changes in rigidity of human natural killer cells.
The success of adoptive immunotherapy is dependent in part on the successful delivery of effector cells to the tumor and the expression of cellular activities, such as adhesion, extravasation, and cytotoxic activity of the effector cells in the tumor. The structural rigidity of the effector cell is an important determinant of these functions. The present study was designed to quantify the changes in cellular rigidity and cytotoxic activity of human natural killer (NK) cells in the presence or absence of interleukin-2 (IL-2). Micropipet aspiration was used to measure the resistance of NK cells to an imposed external deformation. Homogeneous suspensions of NK cells were activated with 1000 U/mL of recombinant IL-2 in vitro and tested for cellular rigidity from 0 to 96 h post stimulation. The IL-2 activated cells increased their rigidity within 24 h and maintained it at this level for 96 h. Prolonged incubation of cells in IL-2 (14 d) resulted in a consistently high rigidity, which was further increased on starvation of the cells from IL-2. The increased rigidity of these cells was maintained throughout 96 h of IL-2 deprivation, although significant relaxation of rigidity was observed between 48 and 96 h. The relaxation of rigidity was associated with an increase in the number of nonviable cells. Reintroduction of IL-2 for 24 h to a culture of NK cells depleted of IL-2 for 48 h did not restore the cells to the pre-depletion level of rigidity. Cytotoxic activity of the activated NK cells following removal of IL-2 decreased to about 60% of the control activity within 24 h and continued through 72 h post-deprivation. These findings suggest that the initial activation of human NK cells by IL-2 will produce a relatively rapid increase in rigidity that may cause entrapment of these cells in small capillaries in vivo and that removal of IL-2 will produce an additional increase in rigidity, which is associated with decreased functional activity.
Melder
R J
RJ
Steele Laboratory for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital, Boston.
Jain
R K
RK
D048429:Cell Size / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D005434:Flow Cytometry; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D010641:Phenotype; D012212:Rheology; D013997:Time Factors
D007376:Interleukin-2