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CD1d-independent NKT cells in beta 2-microglobulin-deficient mice have hybrid phenotype and function of NK and T cells.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2004 May 15; Vol. 172 (10), pp. 6115-22. - Publication Year :
- 2004
-
Abstract
- Unlike CD1d-restricted NK1.1(+)TCRalphabeta(+) (NKT) cells, which have been extensively studied, little is known about CD1d-independent NKT cells. To characterize their functions, we analyzed NKT cells in beta(2)-microglobulin (beta(2)m)-deficient B6 mice. They are similar to NK cells and expressed NK cell receptors, including Ly49, CD94/NKG2, NKG2D, and 2B4. NKT cells were found in normal numbers in mice that are deficient in beta(2)m, MHC class II, or both. They were also found in the male HY Ag-specific TCR-transgenic mice independent of positive or negative selection in the thymus. For functional analysis of CD1d-independent NKT cells, we developed a culture system in which CD1d-independent NKT cells, but not NK, T, or most CD1d-restricted NKT cells, grew in the presence of an intermediate dose of IL-2. IL-2-activated CD1d-independent NKT cells were similar to IL-2-activated NK cells and efficiently killed the TAP-mutant murine T lymphoma line RMA-S, but not the parental RMA cells. They also killed beta(2)m-deficient Con A blasts, but not normal B6 Con A blasts, indicating that the cytotoxicity is inhibited by MHC class I on target cells. IL-2-activated NKT cells expressing transgenic TCR specific for the HY peptide presented by D(b) killed RMA-S, but not RMA, cells. They also killed RMA (H-2(b)) cells that were preincubated with the HY peptide. NKT cells from beta(2)m-deficient mice, upon CD3 cross-linking, secreted IFN-gamma and IL-2, but very little IL-4. Thus, CD1d-independent NKT cells are significantly different from CD1d-restricted NKT cells. They have hybrid phenotypes and functions of NK cells and T cells.
- Subjects :
- Animals
Antigens, CD1d
Cell Differentiation immunology
Cell Lineage genetics
Cell Lineage immunology
Cell Membrane immunology
Cell Membrane metabolism
Cells, Cultured
Dose-Response Relationship, Immunologic
Hybrid Cells cytology
Hybrid Cells metabolism
Interleukin-2 pharmacology
Killer Cells, Lymphokine-Activated cytology
Killer Cells, Lymphokine-Activated immunology
Killer Cells, Natural cytology
Killer Cells, Natural metabolism
Lymphocyte Activation genetics
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
T-Lymphocyte Subsets cytology
T-Lymphocyte Subsets immunology
T-Lymphocyte Subsets metabolism
T-Lymphocytes cytology
T-Lymphocytes metabolism
Antigens, CD1 physiology
Cytotoxicity, Immunologic genetics
Hybrid Cells immunology
Immunophenotyping
Killer Cells, Natural immunology
T-Lymphocytes immunology
beta 2-Microglobulin deficiency
beta 2-Microglobulin genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 172
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 15128797
- Full Text :
- https://doi.org/10.4049/jimmunol.172.10.6115