# Spontaneous somatic Pten loss contributes to functional heterogeneity of T cells

## TL;DR

Healthy mice naturally have T cells with reduced Pten, which affects how these immune cells respond to viral infections.

## Contribution

This study reveals that spontaneous Pten loss in T cells influences their differentiation without causing disease.

## Key findings

- T cells with low Pten expression are common in healthy mice.
- Monoallelic Pten loss biases CD4 T cells toward becoming T follicular helper cells during viral infection.
- This genetic variation does not lead to autoimmune or inflammatory diseases.

## Abstract

We found that healthy mice harbor T cells with heritable low Pten expression and that monoallelic Pten loss in CD4 T cells causes a bias in their differentiation toward T follicular helper cells during acute viral infection. These results suggest that somatically induced mono- or biallelic loss of expression of signaling-related genes in T cells can impact the quality of population-level T cell responses—without conspicuous pathological sequelae such as autoimmune and inflammatory manifestations or lymphomagenesis.

The online version contains supplementary material available at 10.1038/s41598-025-34754-1.