TR1 cells and Malaria

Context

A recent study in Science Immunology has revealed that TR1 cells, a subtype of CD4+ T-helper cells, play a dominant role in the immune response to malaria, challenging the previous belief that TH1 cells were the primary responders. This discovery could lead to new approaches for developing vaccines and therapies for malaria and other challenging infections.

TR1 Cells

TR1 Cells (Type-1 Regulatory T cells) are a subset of CD4+ T cells known for their immunosuppressive functions, primarily mediated by the secretion of IL-10 (Interleukin-10).
These cells are important for tolerogenic immune responses, maintaining immune homeostasis, and preventing excessive inflammation.
However, TR1 cells are present in low frequencies in peripheral blood (~1-10% of memory CD4+ T cells), making their ex vivo isolation and expansion a challenging task.

Clinical Applications & Preclinical Models:

Tolerogenic TR1 Cell Therapy (T-allo10):
- A clinical-grade product called T-allo10 has been developed by co-culturing allo-HSCT (Allogeneic Hematopoietic Stem Cell Transplantation) donor CD4+ T cells with DC-10 cells from the transplant recipient.
- This therapy aims to prevent Graft-versus-Host Disease (GvHD) by promoting alloantigen-specific tolerance.
- T-allo10 is currently undergoing Phase I clinical trials to assess its potential in preventing graft rejection and promoting immune tolerance in transplant patients.

Applications in Clinical Settings

Preventing GvHD:
- Graft-versus-Host Disease (GvHD) is a major complication in allogeneic stem cell transplantation. TR1-enriched cell therapy can induce immune tolerance and prevent GvHD.
- T-allo10 Cells: Co-culture of recipient monocyte-derived DCs with donor CD4+ T cells has shown promising results in preventing GvHD in preclinical studies.
Anti-Leukemia Therapy:
- TR1-like CD4IL-10 cells have been tested for anti-leukemia effects, particularly in AML patients undergoing allo-HSCT. The engineered cells target leukemia cells while maintaining immune tolerance.