Front Vet Sci. 2026 Jun 17;13:1816404. doi: 10.3389/fvets.2026.1816404. eCollection 2026.
ABSTRACT
Effective immunosuppression in large animal models is essential for successful preclinical assessment of cell-based therapies in the allo- or xeno-transplantation setting. Pigs, due to their physiological and immunological similarity to humans, are widely used in translational research. However, direct, longitudinal comparisons of immunosuppressive strategies in swine are scarce, limiting the development of safe and reliable protocols. To address this gap, we performed a head-to-head comparison of two immunosuppressive regimens in pigs (n = 8; 4 animals per group) to identify a protocol that achieves robust immune modulation with minimal systemic toxicity. Protocol I consisted of an intravenous induction with mycophenolate mofetil (MMF) and methylprednisolone, followed by oral MMF and tacrolimus. Protocol II included intravenous abatacept and methylprednisolone, two booster doses of abatacept, and daily oral cyclosporine A. Both regimens were administered for 6 weeks, followed by a four-week recovery period. Statistical analyses included normality testing (Shapiro-Wilk), multiple t-tests or Mann-Whitney tests with false discovery rate correction for between-group comparisons, and two-way repeated measures ANOVA or mixed-effects models for longitudinal analysis. Both protocols induced lymphopenia without systemic toxicity but exhibited distinct immunological profiles. Protocol I promoted rapid and reversible lymphocyte suppression, whereas Protocol II induced a slower onset with sustained inhibitory signaling. Phenotypic analysis revealed dynamic shifts within lymphocyte populations, including a decline in the CD4/CD8 ratio that did not reach statistical significance. CD21+ lymphocytes were differentially affected: Protocol I maintained higher levels after an initial transient decrease, while Protocol II showed a progressive reduction with significant differences at multiple time points. These findings highlight that co-stimulation blockade combined with calcineurin inhibition enforces deeper functional suppression, whereas MMF/tacrolimus-based therapy allows partial recovery of immune compartments. This direct comparative analysis provides a critical framework for designing targeted immunosuppressive strategies for translational models.
PMID:42389690 | PMC:PMC13318597 | DOI:10.3389/fvets.2026.1816404
