TY - JOUR
T1 - Dendritic cells are targets for human invariant Vα24+ natural killer T-cell cytotoxic activity. An important immune regulatory function
AU - Nicol, Andrew
AU - Nieda, Mie
AU - Koezuka, Yasuhiko
AU - Porcelli, Steven
AU - Suzuki, Kenji
AU - Tadokoro, Kenji
AU - Durrant, Simon
AU - Juji, Takeo
N1 - Funding Information:
Supported by the Leukemia Foundation of Queensland, the Queensland Cancer Fund, and The Royal Brisbane Hospital Research Foundation (A.N.).
PY - 2000/3
Y1 - 2000/3
N2 - Objective. Human invariant Vα24+ natural killer T (NKT) cells, a subpopulation of NK cell-receptor (NKR-P1A)-expressing T cells with an invariant Vα24JαQ T-cell receptor (TCR), are stimulated by the glycolipid a-galactosylceramide (KRN7000), in a CD1d-dependent, TCR-mediated fashion. Little is known about invariant Vα24+ NKT cell function or mechanisms of effector activity. Evidence suggests this cell population protects against autoimmunity and has antitumor effects against leukemia and solid tumors. Materials and Methods. We compared the phenotype and function of invariant Vα24+ NKT cells, from patients with chronic myeloid leukemia (CML) and normal donors, generated by stimulation of peripheral blood mononuclear cells with α-galactosylceramide pulsed monocyte-derived dendritic cells. The CD4-CD8- (double negative) population was studied further. Results. Activated human invariant Vα24+ NKT cells were cytotoxic against autologous and allogeneic peripheral blood dendritic cells and monocyte-derived dendritic cells but not against autologous or allogeneic T-cell PHA blasts, B-cell lymphoblastoid cell lines, monocytes, or leukemic cells from patients with CML. The findings are consistent with previous observations showing the importance of CD1d in target cell recognition. None of the Vα24+ NKT cell lines expressed the NK markers CD16, CD56, CD94, or killer inhibitory receptors, but all expressed NKR-P1A. There was no difference in phenotype, function, or ease of generation of invariant Vα24+ NKT cells between normal donors and patients with CML. Conclusion. Based on our results and the previous evidence linking reduced Vα24+ NKT cells to autoimmunity, we propose that double-negative Vα24+ NKT cells have important immune regulatory functions, including contribution to the prevention of excessive antigen stimulation by virtue of cytotoxic activity against antigen presenting cells, particularly in dendritic cells. Copyright (C) 2000 International Society for Experimental Hematology.
AB - Objective. Human invariant Vα24+ natural killer T (NKT) cells, a subpopulation of NK cell-receptor (NKR-P1A)-expressing T cells with an invariant Vα24JαQ T-cell receptor (TCR), are stimulated by the glycolipid a-galactosylceramide (KRN7000), in a CD1d-dependent, TCR-mediated fashion. Little is known about invariant Vα24+ NKT cell function or mechanisms of effector activity. Evidence suggests this cell population protects against autoimmunity and has antitumor effects against leukemia and solid tumors. Materials and Methods. We compared the phenotype and function of invariant Vα24+ NKT cells, from patients with chronic myeloid leukemia (CML) and normal donors, generated by stimulation of peripheral blood mononuclear cells with α-galactosylceramide pulsed monocyte-derived dendritic cells. The CD4-CD8- (double negative) population was studied further. Results. Activated human invariant Vα24+ NKT cells were cytotoxic against autologous and allogeneic peripheral blood dendritic cells and monocyte-derived dendritic cells but not against autologous or allogeneic T-cell PHA blasts, B-cell lymphoblastoid cell lines, monocytes, or leukemic cells from patients with CML. The findings are consistent with previous observations showing the importance of CD1d in target cell recognition. None of the Vα24+ NKT cell lines expressed the NK markers CD16, CD56, CD94, or killer inhibitory receptors, but all expressed NKR-P1A. There was no difference in phenotype, function, or ease of generation of invariant Vα24+ NKT cells between normal donors and patients with CML. Conclusion. Based on our results and the previous evidence linking reduced Vα24+ NKT cells to autoimmunity, we propose that double-negative Vα24+ NKT cells have important immune regulatory functions, including contribution to the prevention of excessive antigen stimulation by virtue of cytotoxic activity against antigen presenting cells, particularly in dendritic cells. Copyright (C) 2000 International Society for Experimental Hematology.
KW - CD1d
KW - Cytotoxic activity
KW - NKR-P1A
KW - Vα24+ natural killer T cells
KW - α-Galactosylceramide
UR - http://www.scopus.com/inward/record.url?scp=0034054027&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034054027&partnerID=8YFLogxK
U2 - 10.1016/S0301-472X(99)00149-6
DO - 10.1016/S0301-472X(99)00149-6
M3 - Article
C2 - 10720692
AN - SCOPUS:0034054027
SN - 0301-472X
VL - 28
SP - 276
EP - 282
JO - Experimental Hematology
JF - Experimental Hematology
IS - 3
ER -