T Cell Metabolism Is Dependent on Anatomical Location within the Lung

The metabolic shift from oxidative phosphorylation to glycolysis is universally accepted as a necessary step for immune cells to mount effector functions. However, it is unknown if this paradigm holds true for T cells regardless of anatomical location. In this study, we compared metabolic responses among distinct mouse pulmonary CD4⁺ effector T cell (T_eff) pools following intranasal vaccination with either Francisella tularensis or Bordetella pertussis Surprisingly, in contrast to circulating CD4⁺ T_eff, upon ex vivo stimulation, resident CD4⁺ T_eff did not shift to glycolysis. This impairment in the resident pool was modestly overcome following in vivo infection. However, consistent with an ex vivo triggered shift toward glycolysis, circulating CD4⁺ T_eff remained superior compared with resident CD4⁺ T_eff after in vivo infection. These data indicate differences in lung T cell metabolism is associated with anatomic location, a feature which may be exploited to enhance or dampen pulmonary T cell responses.