CD4+ T cells promote the transition from hypertrophy to heart failure during chronic pressure overload

Area of Science:

• Immunology
• Cardiology
• Molecular Biology

Background:

• Mechanisms of cardiac adaptation to chronic pressure overload leading to heart failure (HF) remain unclear.
• T cell involvement in HF progression is under investigation.
• Transverse aortic constriction (TAC) is a model for studying pressure overload-induced cardiac changes.

Purpose of the Study:

• To investigate the role of T cells in the progression from cardiac hypertrophy to HF.
• To determine the specific T cell subsets involved in HF pathogenesis.
• To explore the significance of antigen recognition in HF development.

Main Methods:

• Utilized a transverse aortic constriction (TAC) mouse model to induce pressure overload.
• Employed genetically modified mice lacking T and B lymphocytes (RAG2KO), CD4(+) T cells (MHCIIKO), and CD8(+) T cells (CD8KO).
• Assessed cardiac function, dilation, fibrosis, and collagen remodeling post-TAC.

Main Results:

• Chronic HF showed T lymphocyte and activated CD4(+) T cell accumulation in cardiac tissue.
• RAG2KO mice exhibited resistance to TAC-induced cardiac dilation and dysfunction.
• Mice lacking CD4(+) T cells (MHCIIKO) were protected from HF development, unlike CD8KO mice.
• Transgenic CD4(+) T cells specific for ovalbumin prevented HF and adverse remodeling.

Conclusions:

• CD4(+) T cells play a critical role in the transition from compensated hypertrophy to heart failure.
• Specific antigen recognition by CD4(+) T cells is essential for HF progression.
• Targeting CD4(+) T cell activation or specific antigens may offer therapeutic strategies for HF.