Dynamics of Blood-Borne CD8 Memory T Cell Migration In Vivo

Abstract

Memory T cells are distributed throughout the body following infection, but the migratory dynamics of the memory pool in vivo is unknown. The ability of circulating microbe-specific memory T cells to populate lymphoid and nonlymphoid tissues was examined using adoptive transfer and parabiosis systems. While migration of memory CD8 T cells to lymph nodes and peritoneal cavity required G(i)-coupled receptor signaling, migration to the spleen, bone marrow, lung, and liver was independent of this pathway. Following parabiosis, memory T cells rapidly equilibrated into the lymphoid tissues, lung, and liver of each parabiont, implying most memory cells were not obligately tissue resident. Equilibration of memory cell populations was delayed in the brain, peritoneal cavity, and intestinal lamina propria, indicating controlled gating for entry into these tissues. In addition, memory cell migration to the lamina propria required beta7 integrins. Thus, the blood-borne T cell pool serves to maintain the homeostasis of tissue-based memory populations.

Proliferative Expansion and Acquisition of Effector Activity by Memory CD4+ T Cells in the Lungs following Pulmonary Virus Infection

“…As suggested by findings in recent publications (10,11), this population of peripheral memory CD4 ϩ T cells would localize to the lung parenchyma (and other peripheral sites) following primary immunization with the RSV G-expressing vaccinia vector and could potentially respond to challenge RSV infection in situ (i.e., in the infected lungs). Alternately, these findings could also be explained by a mechanism whereby G-specific memory CD4 ϩ V␤14 ϩ T cells present in the recirculating T cell pool would enter the draining PBLN and activate in the PBLN in response to RSV infection.…”

Maintenance of memory T cells in the bone marrow: survival or homeostatic proliferation?

“…This view was in contrast with the largely accepted notion at the time that recirculating memory T cells are maintained by a homeostatic equilibrium between proliferation and death long after antigen clearance 2 . Furthermore, it did not accommodate previous data concerning the proliferation 3,4 and recirculation 5,6 of memory CD8 + T cells in the bone marrow.…”

“…Moreover, global transcription data, CD69 expression profiles and colocalization in tissue sections do not address in vivo T cell migration. In fact, in situ-labelling studies and parabiosis experi ments have shown that memory T cells do recirculate to and from the bone marrow 5,6 .In conclusion, the available evidence supports the view that the bone marrow is a 'stopping point' where recirculating memory CD8 + T cells are stimulated to proliferate before continuing to move around the body 3,4,12,13 . Notably, lodging into the bone marrow is a competitive process among memory T cells 14 , which is an element to be considered especially in interpretation of adoptive transfer data 11,14 .…”

“…Moreover, global transcription data, CD69 expression profiles and colocalization in tissue sections do not address in vivo T cell migration. In fact, in situ-labelling studies and parabiosis experi ments have shown that memory T cells do recirculate to and from the bone marrow 5,6 .…”

Skin TRM mediates distributed border patrol

“…T RM have been found in several tissues, including the skin, gut, lung and brain [3][4][5][6]. Once established, T RM are maintained independently of circulating T EM and T CM and their presence correlates with superior protection against local viral challenge [3,5,7]. However, the exact role of T RM vs. recruited circulating memory T cells in controlling viral replication is unclear.…”