TRI cells/ CD4⁺ cells

Why in News ?. A groundbreaking study published in Science Immunology  recently  has identified TR1 cells as pivotal in the immune response during malaria reinfections.

Relevance : Pre & Mains

Prelims: TCR/TRI cells/ CD4⁺ cells

Mains :  GS 3 ( Science & tech)

• This discovery challenges long-held views about malaria immunity and opens avenues for developing more effective vaccines and host-directed therapies.
• The research highlights the role of TR1 cells in fostering clinical immunity in Ugandan children frequently exposed to malaria.

Key Points of the Study:

Study Focus:

1. • Conducted in eastern Uganda, where malaria is a perennial health concern due to Plasmodium falciparum (Pf).
   • Focused on CD4⁺ T-cells, particularly the regulatory TR1 cells, which account for nearly 90% of Pf-specific helper cells despite forming only 3% of resting CD4⁺ cells.

TR1 Cells – The “Heroes”:

1. • Play a critical role in mounting antigen-specific immune responses to malaria.
   • Exhibit high clonal fidelity and long-term memory, increasing their numbers with each reinfection.
   • These cells assist in developing clinical immunity — individuals become asymptomatic despite recurring infections.

Technique and Methodology:

1. • Utilized advanced tools like single-cell RNA sequencing and T-cell receptor (TCR) sequencing to track helper-cell clones.
   • Adopted a longitudinal study approach, providing a comprehensive view of immune cell behavior over time.

Findings on Immunity:

1. • Contrary to previous beliefs, the TH1 cell response is not malaria-specific.
   • TR1 cells expand after every reinfection and correlate with the parasite load in the blood, reinforcing their Pf-specific role.
   • TR1 cells have distinct subgroups: naïve-like, effector, and memory TR1 cells, confirming their functional diversity and memory potential.

Implications for Vaccines and Therapies:

1. • The study underscores the potential to design vaccines targeting TR1 cells for a more focused immune response.

1. • Introduces the concept of host-directed therapies, which aim to fine-tune the immune system rather than directly attacking the parasite.