Perforin plays an unexpected role in regulating T-cell contraction during prolonged Listeria monocytogenes infection

After infection or vaccination, antigen-specific T cells proliferate then contract in numbers to a memory set point. T-cell contraction is observed after both acute and prolonged infections although it is unknown if contraction is regulated similarly in both scenarios. Here, we show that contraction of antigen-specific CD8 ⁺ and CD4 ⁺ T cells is markedly reduced in TNF/perforin-double deficient (DKO) mice responding to attenuated Listeria monocytogenes infection. Reduced contraction in DKO mice was associated with delayed clearance of infection and sustained T-cell proliferation during the normal contraction interval. Mechanistically, sustained T-cell proliferation mapped to prolonged infection in the absence of TNF; however, reduced contraction required the additional absence of perforin since T cells in mice lacking either TNF or perforin (singly deficient) underwent normal contraction. Thus, while T-cell contraction after acute infection is independent of peforin, a perforin-dependent pathway plays a previously unappreciated role to mediate contraction of antigen-specific CD8 ⁺ and CD4 ⁺ T cells during prolonged L. monocytogenes infection.