Depletion of CD25+ cells restores Th1, Th2 and Th17 responses and mitigates Eimeria maxima infection in chickens

Chicken coccidia can suppress the host immune response through CD4 + CD25 + T cells, compromising the effectiveness of immune prophylaxis and potentially leading to immune failure. However, the role of chicken CD4 + CD25 + T cells in chicken coccidia infection is not well understood. This study aimed to elucidate the immunomodulatory function of CD4 + CD25 + T cells during Eimeria maxima infection and assess the impact of CD25 + cell depletion on immune response and infection outcomes. The study comprised three trials: (1) examining CD4 + CD25 + T cells and cytokine changes post- E. maxima infection, (2) assessing the impact of in vitro CD25 + cell depletion on the immunomodulatory function of peripheral blood mononuclear cells ( PBMCs ) and (3) evaluating the effects of in vivo CD25 + cell depletion on PBMC function and E. maxima infection. The results revealed that E. maxima infection significantly increased CD4 + CD25 + T cell proportions in PBMCs and spleen, along with upregulated mRNA levels of IL-10, TGF-β and IL-4. In vitro CD25 + cell depletion enhanced PBMC proliferation as well as Th1, Th2 and Th17 response. In vivo CD25 + cell depletion partially disrupted E. maxima infection, as evidenced by reduced weight loss, alleviated intestinal lesions, lower oocyst shedding, and an anticoccidial index ( ACI ) exceeding 120. In conclusion, E. maxima infection upregulates CD4 + CD25 + T cells along with their associated cytokines (IL-10 and TGF-β) and the surface molecule CTLA-4; and the depletion of CD25 + cells restores protective Th responses (Th1, Th2 and Th17), while blockade of CD25 in vivo mitigates the E. maxima infection process. This study demonstrates the immunomodulatory role of CD4 + CD25 + T cells during E. maxima infection, providing key insights for elucidating the immune evasion mechanisms of this parasite.