Deficiency of invariant V alpha 14 natural killer T cells decreases atherosclerosis in LDL receptor null mice

Autor: Leah, Rogers, Sarah, Burchat, Jessica, Gage, Mirela, Hasu, Mohamad, Thabet, Lindsay, Willcox, Lindsay, Wilcox, Tanya A, Ramsamy, Stewart C, Whitman
Rok vydání: 2008
Předmět:
Male
CD3 Complex
Physiology
Receptors
Antigen
T-Cell
alpha-beta
T-Lymphocytes
Polymerase Chain Reaction
Antigens
CD1
Mice
Leukocytes
Mice
Knockout
education.field_of_study
hemic and immune systems
Natural killer T cell
Acquired immune system
Interleukin-10
Killer Cells
Natural
medicine.anatomical_structure
Cholesterol
CD1D
Cytokines
Female
Cardiology and Cardiovascular Medicine
Microdissection
medicine.medical_specialty
Histo(patho)logy
T cell
Population
Immunology
Down-Regulation
chemical and pharmacologic phenomena
Biology
Natural killer cell
Interferon-gamma
Immune system
Physiology (medical)
Internal medicine
medicine
Animals
RNA
Messenger
education
Histocompatibility Antigens Class II
Original Articles
Atherosclerosis
Disease Models
Animal
Endocrinology
Receptors
LDL
LDL receptor
biology.protein
Interleukin-4
Antigens
CD1d
Zdroj: Cardiovascular Research
ISSN: 0008-6363
Popis: CD1d-restricted natural killer T (NKT) cells function by regulating numerous immune responses during innate and adaptive immunity. Depletion of all populations of CD1d-dependent NKT cells has been shown by several groups to reduce atherosclerosis in two different mouse models of the disease. In this study, we determined if removal of a single (V alpha 14) NKT cell population protects mice from the disease.Targeted deletion of the J alpha 18 gene results in selective depletion of CD1d-dependent V alpha 14 NKT cells in C57BL/6 mice without affecting the population of other NKT, NK, and conventional T cells. Therefore, to study the effect of V alpha 14 NKT cell depletion on the progression of atherosclerosis, we examined the extent of lesion formation using paired littermate LDL receptor null mice that were either +/+ or -/- for the J alpha 18 gene following the feeding of these mice a cholesterol- and fat-enriched diet for 8 weeks. At the end of the study, we found no difference in either serum total- or lipoprotein-cholesterol distributions between groups. However, quantification of atherosclerosis revealed that V alpha 14 NKT cell deficiency significantly decreased lesion size in the aortic root (20-28%) and arch (28-38%) in both genders of mice. By coupling the techniques of laser capture microdissection with quantitative real-time RT-PCR, we found that expression of the proatherogenic cytokine interferon (IFN)-gamma was significantly reduced in lesions from J alpha 18-/- mice.This study is the first to identify a specific subpopulation of NKT cells that promotes atherosclerosis via a mechanism appearing to involve IFN-gamma expression.
Databáze: OpenAIRE
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