TY - JOUR
T1 - Tumor cell lysis by T cells distinct from NK cells and alloantigen-specific cytotoxic T cells
AU - Thiele, Dwain L
AU - Lipsky, Peter E.
N1 - Funding Information:
The authors thank Melanie Owen and Ruth Pettigrew for excellent technical assistance, and Mrs. Renate Davis and Mrs. Elsa Abraha for preparing the manuscript. This work was supported by Public Health Services Grants AM19329 and AM09989, and by Grant IN-142 from the American Cancer Society. Dr. Thiele is the recipient of NIH Clinical Investigator Award AM01251. and an award from the Clay Weed Memorial Cancer Fund Trust.
PY - 1988/12
Y1 - 1988/12
N2 - The generation and mechanism of tumor cell lysis by cytotoxic T cells derived from natural killer cell (NK) and allospecific cytotoxic T cell (CTL)-depleted precursors were examined. NK cells and the precursors of alloantigen-specific CTL were deleted from human peripheral blood lymphocytes by preincubation with l-leucyl-l-leucine methyl ester (Leu-Leu-OMe). Following phytohemagglutinin activation, CD3(+), CD4(+) or CD8(+), CD11b(-), CD16(-), and NKH1(-) killer cells capable of lysing a broad spectrum of tumor targets were generated. Cytolysis was not strictly lectin dependent as similar killer cells were generated by activating Leu-Leu-OMe-treated T cells with immobilized monoclonal antibodies to the CD3 molecular complex. The rate of tumor cell lysis by these mitogen-activated T cells was slower than that mediated by CD3(-) NK cells. Tumor cell lysis by mitogen-activated killers was inhibited by anti-CD3 but was not restricted by major histocompatibility complex antigen expression on target cells or by CD4/CD8 expression on effectors. Although similar to NK cells in susceptibility to anti-LFA-1 inhibition of killing, these mitogen-activated killer cells were more sensitive to the inhibitory effects of anti-CD2 than were CD3(-)-activated NK-like cells. Thus, tumor cell lysis by CD3(+) cytotoxic cells generated from Leu-Leu-OMe-treated lymphocytes appears to be mediated in part by mechanisms distinct from those employed by CD3(-) NK cells or antigen-specific CTL.
AB - The generation and mechanism of tumor cell lysis by cytotoxic T cells derived from natural killer cell (NK) and allospecific cytotoxic T cell (CTL)-depleted precursors were examined. NK cells and the precursors of alloantigen-specific CTL were deleted from human peripheral blood lymphocytes by preincubation with l-leucyl-l-leucine methyl ester (Leu-Leu-OMe). Following phytohemagglutinin activation, CD3(+), CD4(+) or CD8(+), CD11b(-), CD16(-), and NKH1(-) killer cells capable of lysing a broad spectrum of tumor targets were generated. Cytolysis was not strictly lectin dependent as similar killer cells were generated by activating Leu-Leu-OMe-treated T cells with immobilized monoclonal antibodies to the CD3 molecular complex. The rate of tumor cell lysis by these mitogen-activated T cells was slower than that mediated by CD3(-) NK cells. Tumor cell lysis by mitogen-activated killers was inhibited by anti-CD3 but was not restricted by major histocompatibility complex antigen expression on target cells or by CD4/CD8 expression on effectors. Although similar to NK cells in susceptibility to anti-LFA-1 inhibition of killing, these mitogen-activated killer cells were more sensitive to the inhibitory effects of anti-CD2 than were CD3(-)-activated NK-like cells. Thus, tumor cell lysis by CD3(+) cytotoxic cells generated from Leu-Leu-OMe-treated lymphocytes appears to be mediated in part by mechanisms distinct from those employed by CD3(-) NK cells or antigen-specific CTL.
UR - http://www.scopus.com/inward/record.url?scp=0024246193&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0024246193&partnerID=8YFLogxK
U2 - 10.1016/0090-1229(88)90129-8
DO - 10.1016/0090-1229(88)90129-8
M3 - Article
C2 - 2461269
AN - SCOPUS:0024246193
SN - 0090-1229
VL - 49
SP - 405
EP - 423
JO - Clinical Immunology and Immunopathology
JF - Clinical Immunology and Immunopathology
IS - 3
ER -