Effector T cell differentiation and memory T cell maintenance outside secondary lymphoid organs.
Naive T cell circulation is restricted to secondary lymphoid organs. Effector and memory T cells, in contrast, acquire the ability to migrate to nonlymphoid tissues. In this study we examined whether nonlymphoid tissues contribute to the differentiation of effector T cells to memory cells and the long-term maintenance of memory T cells. We found that CD4, but not CD8, effector T cell differentiation to memory cells is impaired in adoptive hosts that lack secondary lymphoid organs. In contrast, established CD4 and CD8 memory T cells underwent basal homeostatic proliferation in the liver, lungs, and bone marrow, were maintained long-term, and functioned in the absence of secondary lymphoid organs. CD8 memory T cells found in nonlymphoid tissues expressed both central and effector memory phenotypes, whereas CD4 memory T cells displayed predominantly an effector memory phenotype. These findings indicate that secondary lymphoid organs are not necessary for the maintenance and function of memory T cell populations, whereas the optimal differentiation of CD4 effectors to memory T cells is dependent on these organs. The ability of memory T cells to persist and respond to foreign Ag independently of secondary lymphoid tissues supports the existence of nonlymphoid memory T cell pools that provide essential immune surveillance in the periphery.
Section of Nephrology, Department of Internal Medicine, and Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Jagdeep S
JS
Obhrai
Martin H
MH
Oberbarnscheidt
Timothy W
TW
Hand
Lonnette
L
Diggs
Geetha
G
Chalasani
Fadi G
FG
Lakkis
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D006706:Homeostasis; D007156:Immunologic Memory / Q000276:immunology*; D008221:Lymphoid Tissue / Q000166:cytology* / Q000276:immunology*; D051379:Mice; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology*