Natural killer T (NKT) cells are a newly identified unique subset of cells that express both alphabeta T cell receptor and NK cell markers. We investigated the role of NKT cells in modulating adaptive T cell responses in chlamydial infections using human-disease-related chlamydial species. Our study provides in vivo evidence that even closely related pathogens may activate different functional NKT subsets, which can further polarize CD4+ and CD8+ cells in adaptive immune responses.