Background and aims:

Biotechnological therapies have reshaped the management of Ulcerative Colitis by targeting distinct immune pathways; however, their differential effects on peripheral immune homeostasis remain poorly characterized. CD8⁺ T cells, key players in cytotoxic and regulatory responses, undergo dynamic changes in differentiation and activation during inflammation and treatment.

To characterize the peripheral CD8⁺ T-cell subsets in UC patients receiving different biologic agents and to identify treatment-specific immune signatures and potential biomarkers of therapeutic response.

Methods:

Peripheral blood samples from UC patients (n= 13) patients treated with anti-TNF (n=4), Vedolizumab (n=5), or Ustekinumab (n=4), and from biologic-naïve controls (n=5), were analyzed by flow cytometry using panels for T-memory and T-regulatory subsets. CD8⁺ T-cell populations were defined as naïve (CD8+CD45RA+CD95-CD197+), Terminal effector (Teff/TEMRA) (CD8+CD45RA+CD95+CD197-), effector memory (Tem)(CD8+CD45RA-CD95lowCD27-), and central memory (Tcm)(CD8+CD45RA-CD95lowCD27+).

Data were compared using unpaired t-tests to assess differences between treatment groups and controls.

Results:

Compared with controls, Ustekinumab induced a selective modulation characterized by a reduction in naïve (CD8+CD45RA+CD95-CD197+) cells, indicative of a lower proportion of undifferentiated lymphocytes and a shift toward more advanced maturation, and an expansion of effector memory (CD8⁺ CD45RA⁻ CD95lowCD197⁻) and Terminal effector / TEMRA (CD45RA⁻CD62L⁻CD197⁻) subsets (p-value < 0.05). This pattern reflects an increase in differentiated, functionally active CD8⁺ T cells potentially involved in inflammation control and mucosal repair. Such modulation was not observed in patients treated with anti-TNF or Vedolizumab, in whom these subsets remained overall stable.

Conclusions:

These findings indicate IL-12/23 inhibition drives a distinct CD8⁺ T-cell remodeling, reflecting immune adaptation relevant for rapid mucosal healing and long-term therapeutic efficacy. This biologic-specific CD8⁺ T-cell signature may serve as a potential biomarker to predict therapeutic response and guide personalized treatment strategies in IBD.

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