What question did this study set out to answer?

The goal is to understand how immune regulation affects self-reactive Tfh-like CD4+ T cells to prevent autoimmunity.

November 25, 2025The Journal of ImmunologyOpen Access

Immune regulation of naturally occurring self-reactive Tfh-like CD4+ T cells 3068

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Findings demonstrate immune regulation of PD-1/PD-L1 is essential for controlling self-reactive CD4+ Tfh-like cells involved in autoimmunity.

The goal is to understand how immune regulation affects self-reactive Tfh-like CD4+ T cells to prevent autoimmunity.
Examined naturally occurring Tfh-like CD4+ T cells in mice and humans
Investigated the effects of Treg cell depletion on nTfh cells
Utilized antibody blockade of PD-1/PD-L1 and CRISPR/Cas9 to manipulate nTfh cells
Conducted a high-throughput in vivo CRISPR/Cas9 screen for identifying regulatory factors
Identified a population of self-reactive CD4+ T cells with Tfh-like characteristics
Treg depletion mobilizes nTfh cells to non-lymphoid organs
PD-1/PD-L1 blockade causes significant expansion of nTfh cells in vivo
Antibody-mediated and genetic manipulations illustrate the importance of the PD-1/PD-L1 axis for nTfh cell regulation.

Ganci et al. (2025) studied this question.

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Findings demonstrate immune regulation of PD-1/PD-L1 is essential for controlling self-reactive CD4+ Tfh-like cells involved in autoimmunity.