The Absence of Lymphoid CD8+ Dendritic Cell Maturation in L-Selectin−/− Respiratory Compartment Attenuates Antiviral Immunity

Intratracheal instillation of L-selectin-deficient (L-Sel −/− ) mice with an adenovirus 2 (Ad2) vector resulted in the lack of respiratory Ad2- or β-galactosidase-specific CTLs with concomitant long-lived β-galactosidase transgene expression in the lungs. The absence of Ag-specific CTLs was attributed to a deficiency in lymphoid CD11c + CD8 + dendritic cells (DCs) in the lower respiratory lymph nodes (LRLNs). To enable L-Sel −/− CTL activity, cell-sorted L-Sel −/− CD8 + T cells were cocultured with cell-sorted L-Sel +/+ CD8 + or CD8 − DCs or L-Sel −/− CD8 − DCs. Only the CD8 + DCs restored CTL activity; L-Sel −/− CD8 − DCs failed to support L-Sel +/+ CTLs because these remained immature, lacking the ability to express costimulatory molecules CD40, CD80, or CD86. Although no lung CD8 + DCs were detected, the DC environment remained suppressive in L-Sel −/− mice evident by the lack of CTL responses following adenoviral challenge with OVA in recipient L-Sel −/− adoptively transferred with OT-1 CD8 + T cells. To assess whether the L-Sel −/− CD8 − DCs could be induced into maturity, microbial stimulation studies were performed showing the failure of L-Sel −/− LRLN to make matured DCs. When L-Sel −/− mice were subjected in vivo to microbial activation before Ad2 vector dosing, CTL activity was restored stimulating the renewed presence of LRLN CD8 + DCs in L-Sel −/− mice. These studies show that impairment of L-Sel −/− DC maturation results in insufficient mature DCs that require microbial activation to restore increases in respiratory CD8 + DCs to support CTL responses.