CD8+ T cell activation predominate early immune responses to hypercholesterolemia in Apoe⁻(/)⁻ mice.
BACKGROUND
It is well established that adaptive immune responses induced by hypercholesterolemia play an important role in the development of atherosclerosis, but the pathways involved remain to be fully characterized. In the present study we assessed immune responses to hypercholesterolemia induced by feeding Apoe-/- mice a high-fat diet for 4 or 8 weeks.


RESULTS
The primary immune response in lymph nodes draining the aortic root was an increased expression of interferon (IFN)-γ in CD8(+)CD28(+) T cells, while an activation of IFN-γ expression in CD4(+) T cells was observed only after 8 weeks of high-fat diet. Contrarily, spleen CD4(+) T cells responded with a higher expression of IL-10. Spleen CD8(+) T cells expressed both IFN-γ and IL-10 and showed enhanced proliferation when exposed to Concanavalin A. Plasma levels of IgG and IgM against oxidized LDL did not change, but the level of apolipoprotein B/IgM immune complexes was increased.


CONCLUSIONS
Hypercholesterolemia leads to unopposed activation of Th1 immune responses in lymph nodes draining atherosclerotic lesions, whereas Th1 activation in the spleen is balanced by a concomitant activation of Th2 cells. The activation of CD8(+) T cells implies that hypercholesterolemia is associated with formation of cell autoantigens.
Department of Clinical Sciences, Skane University Hospital Malmö, Lund University, Sweden. Daniel.Kolbus@med.lu.se
Daniel
D
Kolbus
Ornélia H
OH
Ramos
Katarina E
KE
Berg
Josefin
J
Persson
Maria
M
Wigren
Harry
H
Björkbacka
Gunilla Nordin
GN
Fredrikson
Jan
J
Nilsson
D000818:Animals; D050197:Atherosclerosis / Q000209:etiology / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018106:CD28 Antigens / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D002791:Cholesterol, Dietary / Q000009:adverse effects; D004036:Diet, Atherogenic; D006937:Hypercholesterolemia / Q000209:etiology / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000235:genetics; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout
D018106:CD28 Antigens; D002791:Cholesterol, Dietary; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D016753:Interleukin-10; D007371:Interferon-gamma