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.

doi:10.64898/2026.02.02.703037

bioRxiv · 10.64898/2026.02.02.703037

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.

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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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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. Diverse Microbial Exposure Enhances CD8+ T Cell Effector Memory Output and Function. https://doi.org/10.64898/2026.02.02.703037

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