PMID- 21978405 OWN - NLM STAT- MEDLINE DCOM- 20120330 LR - 20211020 IS - 1742-2094 (Electronic) IS - 1742-2094 (Linking) VI - 8 DP - 2011 Oct 6 TI - In vivo imaging of lymphocytes in the CNS reveals different behaviour of naive T cells in health and autoimmunity. PG - 131 LID - 10.1186/1742-2094-8-131 [doi] AB - BACKGROUND: Two-photon laser scanning microscopy (TPLSM) has become a powerful tool in the visualization of immune cell dynamics and cellular communication within the complex biological networks of the inflamed central nervous system (CNS). Whereas many previous studies mainly focused on the role of effector or effector memory T cells, the role of naive T cells as possible key players in immune regulation directly in the CNS is still highly debated. METHODS: We applied ex vivo and intravital TPLSM to investigate migratory pathways of naive T cells in the inflamed and non-inflamed CNS. MACS-sorted naive CD4+ T cells were either applied on healthy CNS slices or intravenously injected into RAG1 -/- mice, which were affected by experimental autoimmune encephalomyelitis (EAE). We further checked for the generation of second harmonic generation (SHG) signals produced by extracellular matrix (ECM) structures. RESULTS: By applying TPLSM on living brain slices we could show that the migratory capacity of activated CD4+ T cells is not strongly influenced by antigen specificity and is independent of regulatory or effector T cell phenotype. Naive T cells, however, cannot find sufficient migratory signals in healthy, non-inflamed CNS parenchyma since they only showed stationary behaviour in this context. This is in contrast to the high motility of naive CD4+ T cells in lymphoid organs. We observed a highly motile migration pattern for naive T cells as compared to effector CD4+ T cells in inflamed brain tissue of living EAE-affected mice. Interestingly, in the inflamed CNS we could detect reticular structures by their SHG signal which partially co-localises with naive CD4+ T cell tracks. CONCLUSIONS: The activation status rather than antigen specificity or regulatory phenotype is the central requirement for CD4+ T cell migration within healthy CNS tissue. However, under inflammatory conditions naive CD4+ T cells can get access to CNS parenchyma and partially migrate along inflammation-induced extracellular SHG structures, which are similar to those seen in lymphoid organs. These SHG structures apparently provide essential migratory signals for naive CD4+ T cells within the diseased CNS. FAU - Herz, Josephine AU - Herz J AD - Klinik fur Neurologie, Universitatsklinik Essen, Hufelandstr. 55, 45122 Essen, Germany. FAU - Paterka, Magdalena AU - Paterka M FAU - Niesner, Raluca A AU - Niesner RA FAU - Brandt, Alexander U AU - Brandt AU FAU - Siffrin, Volker AU - Siffrin V FAU - Leuenberger, Tina AU - Leuenberger T FAU - Birkenstock, Jerome AU - Birkenstock J FAU - Mossakowski, Agata AU - Mossakowski A FAU - Glumm, Robert AU - Glumm R FAU - Zipp, Frauke AU - Zipp F FAU - Radbruch, Helena AU - Radbruch H LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20111006 PL - England TA - J Neuroinflammation JT - Journal of neuroinflammation JID - 101222974 RN - 0 (Luminescent Proteins) SB - IM MH - Animals MH - Autoimmunity/*immunology MH - CD4-Positive T-Lymphocytes/*cytology/*immunology/physiology MH - Cell Movement/immunology MH - Cells, Cultured MH - Central Nervous System/*cytology/*immunology MH - Encephalomyelitis, Autoimmune, Experimental/immunology MH - Luminescent Proteins/genetics/metabolism MH - Lymphocyte Activation/immunology MH - Lymphoid Tissue/cytology MH - Mice MH - Mice, Inbred C57BL MH - Mice, Transgenic MH - Microscopy, Confocal/methods MH - T-Lymphocyte Subsets/*cytology/*immunology/physiology PMC - PMC3206448 EDAT- 2011/10/08 06:00 MHDA- 2012/03/31 06:00 PMCR- 2011/10/06 CRDT- 2011/10/08 06:00 PHST- 2011/05/18 00:00 [received] PHST- 2011/10/06 00:00 [accepted] PHST- 2011/10/08 06:00 [entrez] PHST- 2011/10/08 06:00 [pubmed] PHST- 2012/03/31 06:00 [medline] PHST- 2011/10/06 00:00 [pmc-release] AID - 1742-2094-8-131 [pii] AID - 10.1186/1742-2094-8-131 [doi] PST - epublish SO - J Neuroinflammation. 2011 Oct 6;8:131. doi: 10.1186/1742-2094-8-131.