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Department of Microbiology and Carter Immunology Center, University of Virginia, Charlottesville, VA 22908
Exogenous dendritic cells display restricted trafficking when injected in vivo and stimulate CD8 T cell responses that are localized to a small number of lymphoid compartments. By examining these responses in the presence and absence of FTY720, a drug that causes sequestration of T cells in lymph nodes, we demonstrate that a significant fraction of divided CD8 T cells redistribute into Ag-free lymph nodes within 3 days of activation. Despite variation in the level of expression of CD62L, redistribution of these cells is CD62L-dependent. Redistributed CD8 T cells exhibit characteristics of differentiated effectors. However, when re-isolated from Ag-free lymph nodes 3 days after activation and transferred into naive mice, they persist for at least 3 wk and expand upon Ag challenge. Thus, CD8 T cells that redistribute to Ag-free lymph nodes 3 days after immunization contain memory precursors. We suggest that this redistribution process represents an important mechanism for establishment of lymph node resident central memory, and that redistribution to Ag-free nodes is an additional characteristic to be added to those that distinguish memory precursors from terminal effectors.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by United States Public Health Service Grant CA78400 (to V.H.E.), United States Public Health Service Training Grants GM07627 (to S.S.O.), AI007496 and the Robert R. Wagner Fellowship (to C.C.B.), and United States Public Health Service fellowship AI072818 (to A.R.F.).
2 These authors contributed equally to this work and their order should be considered arbitrary.
3 Current Address: Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina 27599.
4 Address correspondence and reprint requests to Dr. Victor H. Engelhard, Carter Immunology Center, University of Virginia, Box 801386, Charlottesville, VA 22908-1386. E-mail address: vhe{at}virginia.edu
5 Abbreviations used in this paper: DC, dendritic cell; LN, lymph nodes; BMDC, bone marrow-derived dendritic cell; TCM, central T memory.
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