Children with acute RV-gastroenteritis (GE) had low or undetectable levels of circulating IFN-gamma(+), IL-13(+), IL-2(+), IL-10(+) or IL-17(+) RV-T cells. IFN-gamma(+) 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-gamma(+)>double IFN-gamma(+)/IL-2(+)>single IL-2(+)RV-CD4(+)T cells were observed in healthy adults. In this group, frequencies of IFN-gamma(+) RV-T cells increased after removing CD25(+)cells, blocking TGF-beta with its natural inhibitor, LAP, or inhibiting TGF-betaRI signalling pathway with ALK5i. The frequencies of IFN-gamma(+) RV-T cells were also incremented in PBMC depleted of CD25(+)cells and treated with ALK5i, suggesting that TGFbeta 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-beta+ Treg cells. Thus, a TGF-beta-mediated regulatory mechanism that modulates RV-T cells in adults is not evident in children.

We studied the interaction of RV with human peripheral blood mononuclear cells (PBMC) from adult volunteers. After exposure of PBMC to rhesus RV (RRV), T and B lymphocytes, NK cells, monocytes, and myeloid and plasmacytoid dendritic cells expressed RV non-structural proteins, at variable levels. Expression of these RV proteins was abolished if infection was done in the presence of anti-VP7 neutralizing antibodies or 10% autologous serum. Supernatants of RRV exposed PBMC contained TNF-alpha, IL-6, IFN-alpha, IFN-gamma, IL-2 and IL-10. Plasmacytoid DC were found to be the main source of IFN-alpha production, and in their absence the production of IFN-gamma and the frequency of RV specific T cells that secrete IFN-gamma diminished. Finally, we could not detect RV-antigen associated with the PBMC or expression of RV non-structural proteins in PBMC of acutely RV-infected children. Thus, although PBMC are susceptible to the initial steps of RV infection, most PBMC of children with RV-gastroenteritis are not infected.

Frequencies of circulating T cells producing IFN-γ, TNF-α, and IL-2, and percentages of T cells proliferating after stimulation with rotavirus (RV), tetanus toxoid, and influenza were evaluated in PBMC derived from healthy adults and children. In addition, the potential anergic state of RV-specific T cells was analyzed by stimulation of PBMC with RV antigen in the presence of three anergy inhibitors (rIL-2, rIL-12, or DGKα-i). The quality and magnitude of RV-T cell responses were significantly lower than those of tetanus toxoid and influenza antigens. RV-CD4 T cell response was enriched in monofunctional IFN-γ(+) cells, while influenza-CD4 and tetanus toxoid-CD4 T cell responses were enriched in multifunctional T cells. Moreover, rIL-2--unlike rIL-12 or DGKα-i--increased the frequencies of RV-CD4 TNF-α(+), CD4 IFN-γ(+), and CD8 IFN-γ(+) cells. Thus, circulating RV-T cells seem to have a relatively poor functional profile that may be partially reversed in vitro by the addition of rIL-2.

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Description of the allergic inflammation.- Comprehension of the early cellular changes after specific immunotherapy has been initiated. Exposure of the mechanisms involved in tolerance induction by regulatory T cells (Treg) with the inhibition of the Th2 responses. Comprehension of IL-10 and transforming growth factor (TGF- ) roles. Explanation of specific IgE, IgG and IgA changes. Description of the suppression of inflammatory responses during immunotherapy.