Activated CD8 T Cells Redistribute to Antigen-Free Lymph Nodes and Exhibit Effector and Memory Characteristics

Abstract

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.

Early simultaneous production of intranodal CD4 Th2 effectors and recirculating rapidly responding central‐memory‐like CD4 T cells

“…NS: non significant. presence of alum, or intratracheal injection of DC [35,[42][43][44][45][46], but the phenotype and responsiveness of these early emigrants had not been characterized within distant Ag-free nodes.…”

“…They have lost the phenotype of naïve cells, for they lack CD45RB while expressing CD44 and CD11a. They express CD62L [35] and in most cases re-express IL-7Ra [47] and are non-proliferating Ki67 cells. These cells also lack the early activation markers CD69 and CD25.…”

“…Previous studies using adoptive transfer of transgenic T cells found that the initial number of transferred cells affects (i) quantitative and qualitative aspects of the T-cell differentiation [33,34], (ii) central and effector memory commitment [20], (iii) survival of T memory cells [21,22], (iv) proliferation, phenotype and acquisition of effector functions [33], (v) expansion, peak and contraction phases of the T-cell immune response [34] as well as (vi) CD62L expression on recirculating T cells [35]. These findings made it necessary to assess whether the appearance of early primed emigrant OT-II cells occurs only in the presence of high numbers of Ag-specific naïve CD4 T cells.…”

Differentiation of Central Memory CD8 T Cells Is Independent of CD62L-Mediated Trafficking to Lymph Nodes

“…Central memory T cells migrating through tertiary tissues adopt effector memory phenotype and function, indicating a high degree of plasticity in memory populations that can be shaped by organ-specific influences (14). In support of this notion, recent studies detected significant numbers of CD62L pos effector T cells in draining lymph nodes early after infection that gave rise to memory T cells at high frequencies (15,16). These findings raise the question as to whether T cells that home frequently to lymph nodes during their transition from effector to memory stages will preferentially adopt central memory phenotype and functional attributes.…”

Human CD4+ effector T lymphocytes generated upon TCR engagement with self-peptides respond defectively to IL-7 in their transition to memory cells

“…[14][15][16][17] In addition, cessation of stimulation has been proposed as a necessary step for effector to memory cell transition. [18][19][20] TCR signalling intensity has been established as a key parameter for memory T-cell formation. Some studies showed that persistent or strong stimulation through the TCR can dampen memory generation.…”