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

Effector T cells generated in mesenteric lymph nodes (mLN) preferentially a ccumulate 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 m echanisms mediating this re-distribution are poorly understood. To study th is, rat T cells from mLN were activated via the T cell receptor and CD28, a nd; injected either intravenously into congenic recipients, or maintained i n culture in the presence of various cytokines. Three days later effector T cells were identified in vivo and in vitro, and surface molecule expressio n and proliferation rate was determined. The data show that in vivo effecto r mLN T cells express significantly higher levels of activation markers and maintain a higher proliferation rate after entering the mLN environment (t issue of origin) than after entering the peripheral LN environment (unrelat ed site). The proliferation is mediated by TGF beta -1 and IL-4 present in mLN. The requirement for these cytokines is imprinted on effector mLN T cel ls 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 immun e response.