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Diverse Microbial Exposure Enhances CD8+ T Cell Effector Memory Output and Function

Thefaine, C. E.; Lucas, E. D.; Block, K. E.; Pierson, M.; Dehm, E.; Huggins, M.; Casey, O. W.; Zemmour, D.; Jameson, S. C.; Hamilton, S. E.

2026-02-04 immunology
10.64898/2026.02.02.703037 bioRxiv
Show abstract

Mice with normalized microbial exposure (NME) harbor an immune system that more accurately reflects that of humans compared to mice maintained as specific pathogen-free (SPF). An explanation for the observed alterations in the composition of the T cell compartment in NME mice has not been reported. We compared the T cell landscape in NME versus SPF mice at baseline and after acute LCMV infection. Using the immgenT dataset, we found no unique T cell populations in NME, but the landscape shifted towards activated T cells with increased propensity for effector functions and improved pathogen clearance. CD8+ KLRG1+ cells (immgenT CD8_cl12) are significantly expanded in NME mice. Their predominance was a result of both increased formation and the conversion of other memory populations to a KLRG1+ phenotype. Thus, NME mice provide insight into a diverse T cell compartment rich with cells previously found to be limited in SPF mice.

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