CD45RC isoform expression identifies functionally distinct T cell subsets differentially distributed between healthy...

Area of Science:

• Immunology
• Autoimmunity
• T cell subsets

Background:

• CD45RC T cell subsets are crucial in animal models of ANCA-associated vasculitis (AAV).
• The functional roles of human CD45RC T cell subsets remain poorly understood.
• Understanding these subsets is key to deciphering AAV pathogenesis.

Purpose of the Study:

• To investigate the distribution and function of human CD45RC T cell subsets.
• To compare these subsets in healthy controls (HC), AAV patients, and Systemic Lupus Erythematosus (SLE) patients.
• To determine if CD45RC T cell subset imbalance is associated with AAV.

Main Methods:

• Flow cytometry was used to analyze CD45RC expression on human CD4 and CD8 T cells.
• Cytokine profiles of purified CD45RC T cell subsets were assessed following stimulation.
• Patient cohorts included HC, AAV patients, and SLE patients.

Main Results:

• CD45RC expression defines highly variable human CD4 and CD8 T cell subsets.
• AAV patients showed a significantly increased proportion of CD45RC(low) CD4 T cells compared to HC and SLE patients.
• This imbalance was stable over time and independent of disease characteristics.
• CD45RC(low) T cells produced IL-17, IL-4, IL-5, and IL-10, while all subsets produced type-1 cytokines.

Conclusions:

• CD45RC expression delineates functionally distinct human T cell subsets.
• An imbalance in these subsets, particularly elevated CD45RC(low) CD4 T cells, is characteristic of AAV.
• This stable, pre-existing immune abnormality is hypothesized to play a role in AAV etiology.