Neonatal BCG vaccination induces IL-10 production by CD4+ CD25+ T cells

Abstract

To determine the optimal time of Bacillus Calmette-Guerin (BCG) vaccination for induction of Th1 immunity, we measured the interferon (IFN)-γ and interleukin (IL)-10 secretion in purified protein derivative (PPD)-stimulated peripheral blood mononuclear cell (PBMC) cultures in newborns vaccinated at birth or 2nd month of life. Moreover, role of CD4(+) CD25(+) T cells was studied by depletion assay at 8th month. Nineteen term and healthy newborns were randomized into two groups: Group I composed of 10 newborns vaccinated with BCG at birth and the remaining 9 (group II) at 2nd month of life. PBMCs were isolated at birth, 2nd and 8th months of age, and PPD-stimulated IL-10, 5 and IFN-γ secretion were assessed. The same measurements were repeated for IL-10 and IFN-γ after the depletion of CD4(+) CD25(+) T cells at the 8th month. Children vaccinated at birth demonstrated higher PPD-stimulated IFN-γ and IL-10 levels at 2 months of age when compared to non-vaccinated ones (p = 0.038 and p = 0.022, respectively), whereas at 8 months, no significant differences were detected between the two groups. Moreover, CD4(+) CD25(+)-depleted T-cell cultures resulted in lower PPD-stimulated IL-10 levels in those vaccinated at birth when compared to non-depleted condition at the 8th month (p < 0.001). BCG at birth upregulated PPD-stimulated IFN-γ secretion at the 2nd month and remained still detectable at 8 month after the vaccination, whereas those vaccinated at the 2nd month of life lacked that increase in IFN-γ response at the same time-point. Furthermore, depletion assays suggest that CD4(+) CD25(+) T cells are involved in PPD-stimulated IL-10 secretion in response to BCG vaccination.

Treatment of Disseminated Mycobacterial Infection with High-Dose IFN-γin a Patient with IL-12Rβ1 Deficiency

“…Recent studies showed that giving BCG vaccine at birth induces significant mycobacterial immune response as early as 2 months of life. When this response was tested at about 9 months of age it was found to be maintained and comparable to infants who received the vaccine at 2 or 4.5 months of life [12, 13]. …”

Future Path Toward TB Vaccine Development: Boosting BCG or Re-educating by a New Subunit Vaccine

“…It is possible that priming with BCG induced T regs , which then dampened the induction of responses against LP-ESAT-6. It has been shown earlier that BCG vaccine triggers the specific activation of CD4 + and CD8 + T regs (43)(44)(45). However, to what extent the T regs affect boosting with another vaccine is not clear, and we did not evaluate them in our experiments as we performed all of our studies in mice with productive infection with Mtb.…”

Soluble Mediators Regulating Immunity in Early Life

“…Conversely, IL-10 also enhances antibody (Ab) production by promoting B-cell survival and differentiation and increasing the production of IgG4 Abs (13). IL-10 enhances generation of regulatory T cells (Tregs) that inhibit a neonatal immune response to BCG (16, 19). How elevated levels of IL-10 affect neonatal defense against other pathogens is unclear, but is likely context dependent.…”