Changes in homing receptor expression on murine lymphokine-activated killer cells during IL-2 exposure.
The effects of IL-2 on the expression of homing receptors by lymphocytes of NK or lymphokine activated killer (LAK) cell derivation has not yet been evaluated. We developed a murine model to evaluate the potential of LAK cells to localize into peripheral lymph nodes since LAK cells are used to treat human cancers which have metastasized to these tissues. Using a frozen section binding assay, LAK cell adhesion to the lymph node microvasculature was easily demonstrable. Inhibition studies demonstrated that LAK cell binding to lymph nodes was mediated by mechanisms previously described in T cells. LAK cell surface expression of the 85- to 95-kDa homing receptor recognized by the antibody MEL-14 on LAK cells was assessed by indirect immunofluorescence. The percentage of cells which bound MEL-14 decreased slightly over 3 days of IL-2 exposure (from 73 to 60%), particularly in the large granular lymphocyte (cytotoxic effector) subpopulation (45% MEL-14+). The expression of another homing-related molecule, leukocyte function-associated Ag-1, markedly increased during activation of LAK cells. Despite the expression of these homing receptors, we observed almost no LAK cell localization into lymph nodes in vivo. Furthermore, IL-2 pretreatment of recipient animals did not increase the adhesion of LAK cells to lymph node microvasculature or enhance their extravasation. IL-2 activation of non-T, non-B lymphocytes results in significant changes in both the expression and function of cell surface homing receptors. Our results indicate that in vitro analysis does not always predict in vivo localization potential.
Steen
P D
PD
Salt Lake City Veterans Administration Medical Center, UT.
McGregor
J R
JR
Lehman
C M
CM
Samlowski
W E
WE
D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D000954:Antigens, Surface / Q000378:metabolism; D002448:Cell Adhesion / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D003602:Cytotoxicity, Immunologic; D004729:Endothelium, Lymphatic / Q000276:immunology; D007376:Interleukin-2 / Q000494:pharmacology*; D015979:Killer Cells, Lymphokine-Activated / Q000378:metabolism*; D008198:Lymph Nodes / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D011971:Receptors, Immunologic / Q000378:metabolism*; D016028:Receptors, Leukocyte-Adhesion / Q000378:metabolism; D016201:Receptors, Lymphocyte Homing
D000943:Antigens, Differentiation; D000954:Antigens, Surface; D015815:Cell Adhesion Molecules; D007376:Interleukin-2; D016169:Lymphocyte Function-Associated Antigen-1; D011971:Receptors, Immunologic; D016028:Receptors, Leukocyte-Adhesion; D016201:Receptors, Lymphocyte Homing