Genetically programmed biases in Th1 and Th2 immune responses modulate atherogenesis

Area of Science:

• Immunology
• Cardiovascular Research
• Atherosclerosis Pathogenesis

Background:

• T lymphocytes play a crucial role in adaptive immunity and innate immune regulation within atherosclerotic lesions.
• Different T helper cell subsets, specifically Th1 and Th2, have distinct roles in immune responses.
• Genetic background can influence T-cell polarization, impacting immune responses.

Purpose of the Study:

• To investigate the differential impact of Th1 and Th2 helper T-cell responses on the development of atherosclerosis.
• To compare atherogenesis in two mouse strains with opposite T-cell subset polarizations (Apolipoprotein E knockout C57BL/6 vs. BALB/c).
• To determine if immune responses modulate atherosclerosis independently of lipid levels.

Main Methods:

• Utilized two strains of Apolipoprotein E knockout (ApoE-/-) mice: C57BL/6 (prone to Th1 responses) and BALB/c (prone to Th2 responses).
• Administered a high-cholesterol diet to both mouse strains for 10, 16, and 24 weeks.
• Assessed atherosclerosis development in the aortic root and abdominal aorta, and measured serum levels of interleukin-6 (IL-6) and serum amyloid A (SAA).

Main Results:

• ApoE-/- BL/6 mice, exhibiting a Th1-biased immune response, developed significantly more atherosclerosis than ApoE-/- BALB/c mice with a Th2 bias.
• Th1-polarized mice showed higher levels of IgG2a antibodies to oxidized low-density lipoprotein, while Th2-polarized mice produced IgG1 antibodies.
• Increased atherosclerosis correlated with elevated serum IL-6 and SAA levels, particularly in the Th1-prone BL/6 mice, suggesting a link between inflammation and disease progression.

Conclusions:

• A Th1-dominant immune response promotes atherogenesis, highlighting a pro-atherogenic role for Th1 cells.
• Genetic factors influencing immune responses can modulate atherosclerosis progression independently of systemic cholesterol levels.
• Circulating IL-6 and SAA may serve as indicators of altered Th1/Th2 balance and inflammatory activity in atherosclerosis.