OX40 controls functionally different T cell subsets and their resistance to depletion therapy

Area of Science:

• Immunology
• Transplantation Immunology

Background:

• T cell depletion is crucial in transplantation but leaves resistant T cells.
• The characteristics and resistance mechanisms of these persistent T cells are not well understood.

Purpose of the Study:

• To investigate the phenotype and function of T cells resistant to anti-lymphocyte serum (ALS) depletion.
• To elucidate the role of OX40 in the survival and function of these resistant T cells.

Main Methods:

• Analysis of CD4(+) T cells resistant to ALS depletion in mice.
• Phenotypic characterization including OX40 and Foxp3 expression.
• Adoptive transfer experiments into Rag(-/-) mice to assess allograft rejection.
• Functional assays involving OX40 stimulation.

Main Results:

• ALS-resistant CD4(+) T cells exhibit memory cell phenotype and express OX40.
• These resistant cells include both Foxp3(+) regulatory T cells (Tregs) and Foxp3(-) T effector/memory cells.
• While OX40 is vital for the survival of both Tregs and effector cells, it differentially impacts their function: enhancing effector cell proliferation but impairing Treg suppressor function.
• Removal of Tregs from the OX40(+) population led to prompt skin allograft rejection.

Conclusions:

• OX40 is a key regulator of survival and function in T cells resistant to depletion therapies.
• Targeting OX40 may offer a strategy to modulate the immune response in transplantation.