Lysis of endothelial cells by autologous lymphokine-activated killer cells.
The mechanisms of lysis of endothelial cells derived from human umbilical vein (HUVEC) by autologous lymphokine-activated killer (LAK) cells, generated from cord blood lymphocytes of the same donor, were investigated. Freshly isolated HUVEC as well as HUVEC cultured for several passages were efficiently lysed by autologous LAK cells, and their susceptibility to the LAK cells was almost the some as that of allogenic HUVEC. Complement-depletion experiments revealed that the lysis was mainly dependent on CD16+ natural killer (NK) LAK cells. pretreatment of HUVEC with recombinant interferon gamma (rIFN gamma) for 24 h made them resistant to lysis by autologous LAK cells, while pretreatment with either rIL-1 beta. rTNF alpha, or acidic or basic fibroblast growth factor did not alter the lytic sensitivity of HUVEC. The resistance of rIFN gamma-treated HUVEC was specific to lysis by CD16+ NK LAK cells, and their lysis by CD3+ T-LAK cells was not significantly altered. Moreover, in comparison with control HUVEC or rIL-1 beta-treated HUVEC, rIFN gamma-treated HUVEC had a significantly less potent inhibitory effect on the lysis of untreated HUVEC, when used as an unlabeled target. This suggests that rIFN gamma treatment may down-regulate the recognition of some molecules on HUVEC by rIL-2-activated NK cells. These data suggest that damage of the endothelium during LAK therapy is mainly dependent on LAK cells with a NK phenotype that can specifically recognize a certain molecule on autologous endothelial cells.
Kitayama
J
J
First Department of Surgery, University of Tokyo, Japan.
Tsuno
N
N
Yasuhara
H
H
Nagawa
H
H
Kimura
W
W
Kuroda
A
A
Shibata
Y
Y
Juji
T
T
Muto
T
T
D017252:CD3 Complex / Q000276:immunology; D002478:Cells, Cultured; D003165:Complement System Proteins / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D004730:Endothelium, Vascular / Q000378:metabolism*; D005312:Fetal Blood / Q000166:cytology; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000009:adverse effects; D015979:Killer Cells, Lymphokine-Activated / Q000378:metabolism*; D009369:Neoplasms / Q000628:therapy; D017452:Receptors, IgG / Q000276:immunology; D013997:Time Factors; D014471:Umbilical Veins
D017252:CD3 Complex; D016207:Cytokines; D017452:Receptors, IgG; D003165:Complement System Proteins