A TGF-β mediated regulatory mechanism modulates the T cell immune response to rotavirus in adults but not in children

Children with acute RV-gastroenteritis (GE) had low or undetectable levels of circulating IFN-γ⁺, IL-13⁺, IL-2⁺, IL-10⁺ or IL-17⁺ RV-T cells. IFN-γ⁺ T cells and low frequencies of IL-10⁺ and IL-2⁺ CD4⁺ T cells were found in adults with RV-GE during acute and convalescence phases, respectively. Circulating single IFN-γ⁺ > double IFN-γ⁺/IL-2⁺ > single IL-2⁺RV-CD4⁺T cells were observed in healthy adults. In this group, frequencies of IFN-γ⁺ RV-T cells increased after removing CD25⁺cells, blocking TGF-β with its natural inhibitor, LAP, or inhibiting TGF-βRI signalling pathway with ALK5i. The frequencies of IFN-γ⁺ RV-T cells were also incremented in PBMC depleted of CD25⁺cells and treated with ALK5i, suggesting that TGFβ inhibition may be independent of Treg cells. The ALK5i effect was observed in adults but not in children with RV-GE, who had normal numbers of TGF-β+ Treg cells. Thus, a TGF-β-mediated regulatory mechanism that modulates RV-T cells in adults is not evident in children.