Fig. 5

CD4⁺ CTLs in various diseases. CD4⁺ CTLs play pivotal roles in various disease contexts. In cancer, CD4⁺ CTLs assist the immune system in recognizing and eliminating tumor cells, particularly those expressing MHC class II molecules, as these cells often evade clearance by CD8⁺ CTLs through immune escape. The unique feature of CD4⁺ CTLs helps fill this functional gap. In infectious diseases, CD4⁺ CTLs serve as a key defense mechanism against both viral and bacterial pathogens, using their cytotoxic capabilities to clear infected cells and help control the spread of infection. However, in autoimmune diseases, the activation of CD4⁺ CTLs can become dysregulated, leading to excessive tissue damage and inflammation, thus worsening the progression and severity of the disease. In cardiovascular diseases, the activation of CD4⁺ CTLs may lead to immune-mediated myocardial or vascular tissue damage, resulting in functional abnormalities and pathological damage. MICA MHC class I chain-related protein A, GM-CSF granulocyte‒macrophage colony‒stimulating factor, M-CSF macrophage colony‒stimulating factor, GPR56 G protein‒coupled receptor 56, HVs hepatitis viruses, HIV human immunodeficiency virus, SARS-CoV-2 severe acute respiratory syndrome coronavirus 2, HTR heart transplant rejection, AF atrial fibrillation, CAD coronary artery disease, GCA giant cell arteritis, SLE systemic lupus erythematosus, RA rheumatoid arthritis, IBD inflammatory bowel disease. Created at https://BioRender.com