The immunoregulatory role of CD4+FoxP3+CD25-regulatory T cells in lungs of mice infected with Bordetella pertussis

The identification of regulatory T (Treg) cells was originally based on CD25 expression; however, CD25 is also expressed by activated effector T cells. FoxP3 is a more definitive marker of Treg cells, and CD4+FoxP3+CD25+ T cells are considered the dominant natural Treg (nTreg) population. It has been suggested that certain CD4+FoxP3+ Treg cells do not express CD25. In this study, we used a murine model of respiratory infection with Bordetella pertussis to examine the role of Treg cells in protective immunity in the lung. We first demonstrated that CD4+FoxP3+CD25- cells are the dominant Treg population in the lung, gut and liver. Pre-activated lung CD4+FoxP3+CD25- cells suppressed CD4+ effector T cells in vitro, which was partly mediated by IL-10 and not dependent on cell contact. Furthermore, CD4+FoxP3+CD25-IL-10+ T cells were found in the lungs of mice at the peak of infection with B. pertussis. The rate of bacterial clearance was not affected by depletion of CD25+ cells or in IL-10-deficient (IL-10-/-) mice, but was compromised in CD25-depleted IL-10-/- mice. Our findings suggest that IL-10-producing CD4+FoxP3+CD25- T cells represent an important regulatory cell in the lung.