The expression of early resistance to an infection with Mycobacterium tuberculosis by old mice is dependent on IFN type II (IFN-γ) but not IFN type I

Abstract

Old mice can express a transient early resistance to infection with M. tuberculosis that requires the presence of CD8 T cells within the lungs. Further characterization of those CD8 T cells within the aged lung established that the majority of CD8 T cells from old mice expressed the IL-15 receptor (CD122) in combination with bright expression of CD44 (CD44 hi), and were capable of producing IFN-γ after T cell receptor cross-linking. It has been previously described that CD8 CD44 hi T cells proliferate in response to IFN-I, acting via IL-15, and therefore we determined whether IFN-I signaling could be a participant in the response of CD8 T cells within the lungs of old mice infected with M. tuberculosis. We demonstrate here that IFN-I signaling was required for the expansion of CD8 T cells within the aging lung in response to infection with M. tuberculosis, but that IFN-I signaling had no influence on the capacity of old mice to express early resistance to an infection with M. tuberculosis. Resident CD8 T cells were still however capable of producing IFN-γ, which we demonstrate here to be critical in the expression of early resistance, suggesting that the expression of early resistance requires the participation, but not expansion, of the CD8 T cell pool within the aging lung.