CD۴⁺ and CD۸⁺ T-Cell Downregulation as a Hallmark of Immune Dysfunction in Canine Distemper Virus Infection

Background: Canine distemper virus (CDV) is a highly contagious, pantropic morbillivirus that affects multiple systems in dogs, from respiratory, gastrointestinal, neurological, and immune systems, leading to immune suppression and severe clinical outcomes; Yet, the extent of T-cell dysregulation remains insufficiently characterized. This study examined immune responses in CDV-infected dogs using a (para)clinical diagnostic score-based design. Methods: sixteen dogs were classified as either CDV-positive (n=۸) or healthy/control (n=۸). CDV-infected dogs were subsequently divided into mild (n=۴) and severe (n=۴) groups based on clinical scores. RT-qPCR was performed to assess mRNA expression levels of CD۴ and CD۸ in blood leukocytes of healthy and CDV-positive dogs confirmed by physical examination and immunochromatography assays. Results: CDV infection resulted in significant downregulation of key immune molecules CD۴ and CD۸ (P<۰.۰۰۰۱) in both the mild and severe groups compared to controls. Conclusion: The down-regulation of CD۴+ and CD۸+ T cells may significantly contribute to the pathogenesis of CDV, impacting immune response and disease progression. Emerging evidence from human and experimental models suggests that restoring T-cell function through immunotherapeutic interventions - such as immune checkpoint inhibitors targeting PD-۱/PD-L۱, metabolic reprogramming, and epigenetic modulation - can reverse CD۸⁺ exhaustion and reestablish antiviral immunity. Combination approaches incorporating ICIs with agents like p۳۸ MAPK inhibitors have shown additive effects in enhancing T-cell proliferation and functionality. Although these strategies remain unexplored in CDV treatment regimens, modulation of CD۴⁺ and CD۸⁺ pathways may represent a promising avenue to counteract immune collapse and improve outcomes in severe CDV infection.

کلیدواژه ها:

CD۴ ، CD۸ ، RT-qPCR ، Immune dysregulation ، Canine distemper virus