During type 1 immune responses, CD4 T helper 1 (Th1) cells and CD8 T cells are activated via IL-12 and contribute to the elimination of intracellular pathogens through interferon gamma (IFNγ) production. In this study, we identified Placenta-specific 8 (Plac8) as a gene that is uniquely expressed in Th1 CD4 T cells relative to other CD4 T cell subsets and hypothesized that Plac8 may represent a novel therapeutic target in Th1 CD4 T cells. First, we determined that Plac8 mRNA in CD4 T cells was induced following IL-12 stimulation via an indirect route that required new protein synthesis. Upon evaluating the functional relevance of Plac8 expression in Th1 CD4 T cells, we discovered that Plac8 was important for suppressing IFNγ mRNA and protein production by CD4 T cells 24 hours after IL-12 stimulation, however Plac8 did not contribute to pathogenic CD4 T cell function during two models of intestinal inflammation. We also noted relatively high basal expression of Plac8 in CD8 T cells which could be further induced following IL-12 stimulation in CD8 T cells. Furthermore, Plac8 expression was important for establishing an optimal CD8 T cell response against influenza A virus via a T cell-intrinsic manner. Altogether, these results implicate Plac8 as a potential regulator of Th1 CD4 and CD8 T cell responses during Th1 T cell-driven inflammation.

Heterosubtypic CD8 T cell immunity can protect mice and humans against reinfection with highly mutagenic viruses like influenza. Studies in mice attribute this protection to CD8+ tissue resident memory cells (TRM) residing in the lung and airways. However, both live attenuated influenza vaccines and natural influenza infection fail to protect humans from seasonal influenza. Interestingly, unlike TRM derived from other mucosal infections, the majority of TRM in the lung parenchyma are devoid of CD103 and CD69 expression, suggesting bona-fide TRM are either not generated or stably maintained. Using a mouse model, we show respiratory infection evokes the selective migration of CD11c+CD11b+CD103+CCR2+PD-L1hi moDCs to the lung-draining lymph nodes in response to a variety of pathogens (influenza, RSV, VSV) 72–96 hours post infection, coordinate with T cell priming. These moDC develop in the context of systemic and intranasally VSV challenged animals and influenza infected mice, but only emigrate from the bone marrow after respiratory infection. Lymph node immigration is coordinate with regional CCL2 expression. Importantly, the selective depletion of moDCs using CCR2-DTR bone marrow chimeras numerically enhances CD103+CD69+ TRM formation and increases local IFN-ɣ and TNF-α after heterologous virus challenge. In summary, our studies show that moDCs selectively suppress TRM formation after respiratory infection. Ongoing studies seek to understand the molecular mechanism(s) used by moDCs to alter CD8 T cell programming and TRM development.