Table 3.

Comparison of CD4+ vs. CD8+ T Cell Subtypes in CAR T-Cell Therapy.

Feature	CD4+ T Cells	CD8+ T Cells
Role in Immunity	Primarily help activate other immune cells; provide support and enhance the immune response.	Primarily responsible for directly killing infected or cancerous cells.
Outcomes in Therapy	Enhance overall immune response, can contribute to more sustained disease control when included.	Often more effective at rapid tumor clearance; essential for immediate cytotoxic activity.
Proliferative Capacity	Generally lower proliferative capacity compared to CD8+ T cells but crucial for long-term immunological support and memory.	Higher proliferative capacity, crucial for immediate antitumor activity.
Persistence	Longer persistence in the body, which helps in maintaining a prolonged immune response against cancer cells.	Shorter persistence than CD4+ cells, but efforts to engineer longer-lasting CD8+ cells are ongoing.
Therapeutic Efficacy	Important for cytokine production and helping CD8+ T cells function optimally. Often engineered in CAR T-cell therapies for balanced responses.	Typically show higher efficacy in terms of direct tumor cell destruction in the short term. Used predominantly in most CAR T-cell constructs.
Synergistic Potential	Synergize with CD8+ T cells to enhance and sustain antitumor response. Can be engineered to help modulate the tumor microenvironment.	Synergy with CD4+ T cells enhances their effectiveness and longevity in the host.
Clinical Implications	Enhancements in CD4+ CAR T-cell designs are aimed at improving their antitumor functions and persistence, reflecting their role in achieving durable remissions.	Focus on enhancing the cytotoxic capacity and persistence to improve immediate and long-term clinical outcomes.