Gut-derived effector T cells circulating in the blood of the rat: Preferential re-distribution by TGFβ-1 and IL-4 maintained proliferation

Effector T cells generated in mesenteric lymph nodes (mLN) preferentially accumulate in mLN and sites drained by them, such as Peyer's patches and the lamina propria of the gut, after circulation in the blood. The molecular mechanisms mediating this re-distribution are poorly understood. To study this, rat T cells from mLN were activated via the T cell receptor and CD28, and injected either intravenously into congenic recipients, or maintained in culture in the presence of various cytokines. Three days later effector T cells were identified in vivo and in vitro, and surface molecule expression and proliferation rate was determined. The data show that in vivo effector mLN T cells express significantly higher levels of activation markers and maintain a higher proliferation rate after entering the mLN environment (tissue of origin) than after entering the peripheral LN environment (unrelated site.) The proliferation is mediated by TGFβ-1 and IL-4 present in mLN. The requirement for these cytokines is imprinted on effector mLN T cells during the initial activation. Thus, the preferential proliferation of effector mLN T cells in milieus providing the cytokine mixture experienced during activation ensures a privileged accumulation at sites where they are most needed. This can be used to manipulate the effector phase of an immune response.