Anatomical heterogeneity of memory CD4+ T cells due to reversible adaptation to the microenvironment.
The memory T cell pool is characterized by a substantial degree of heterogeneity in phenotype and function as well as anatomical distribution, but the underlying mechanisms remain unclear. In this study we confirm that the memory CD4(+) T cell pool in wild-type and TCR-transgenic mice consists of heterogeneous subsets, as defined by surface marker expression or cytokine production. Extralymphoid sites contain significant numbers of memory CD4(+) T cells, which are phenotypically and functionally distinct from their lymphoid counterparts. However, we show in this study that the phenotype of lymphoid and extralymphoid memory T cells is not stable. Instead, the unique properties of extralymphoid memory T cells are acquired upon migration into extralymphoid sites and are lost when memory T cells migrate back into lymphoid organs. Thus, at least some of the extralymphoid properties may represent a transient activation state that can be adopted by T cells belonging to a single memory T cell pool. Furthermore, such intermittent activation during or after migration into extralymphoid sites could provide an important signal, promoting the survival and functional competence of memory T cells in the absence of Ag.
Kassiotis
George
G
Division of Molecular Immunology, National Institute for Medical Research, London, United Kingdom.
Stockinger
Brigitta
B
D000222:Adaptation, Physiological / Q000235:genetics / Q000276:immunology*; D019264:Adoptive Transfer; D000595:Amino Acid Sequence; D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000637:transplantation; D007156:Immunologic Memory / Q000235:genetics; D016130:Immunophenotyping; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010529:Peritoneal Cavity / Q000166:cytology; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation