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More MS news articles for October 2002

Migration and differentiation of CD8+ T cells

Immunol Rev 2002 Aug;186(1):221-33
Weninger W, Manjunath N, Von Andrian UH.
Authors' addressesWolfgang Weninger, N. Manjunath,Ulrich H. von Andrian,The Center for Blood Research and Departments of Pathology and Pediatrics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.

Antigen-specific responses by CD8+ T cells require direct cell-cell interactions between T cells and antigen-presenting cells (APC).

Initially, naive T cells must communicate with APC in lymphoid organs.

Once stimulated, the resulting effector cells interact with APC in peripheral tissues.

To this end, T cells must migrate to discrete sites throughout the body where antigen may be found.

Recent progress in the field has revealed that the migratory abilities of T cells are critically dependent on their differentiation state, which is shaped by a multitude of factors.

Thus, naive T cells are normally restricted to recirculate between the blood and secondary lymphoid tissues, although in some autoimmune diseases they may also accumulate in chronically inflamed tissues.

When CD8+ T cells encounter antigen and differentiate into short-lived effector CTL, they lose the ability to home to lymph nodes but gain access to peripheral tissues and sites of inflammation.

Long-lived memory cells exist in (at least) two flavors: central memory cells that migrate to both lymphoid organs and peripheral sites of inflammation, and effector memory cells that are preferentially localized in non-lymphoid tissues.

Our current understanding of the interplay of T cell differentiation and migration has been boosted by the development of T-GFP mice, in which transgenic green fluorescent protein is expressed selectively in naive and central memory T cells, but not in effector cytotoxic T cells (CTL).

This review will focus on recent studies in which T-GFP mice were used to dissect the traffic signals for naive T cell homing to secondary lymphoid organs, the factors that influence the differentiation of naive CD8+ T cells into cytotoxic and memory cells, as well as the in vivo trafficking routes of antigen-experienced subsets.