Brain antigens in functionally distinct antigen-presenting cell populations in cervical lymph nodes in MS and EAE

Drainage of central nervous system (CNS) antigens to the brain-draining cervical lymph nodes (CLN) is likely crucial in the initiation and control of autoimmune responses during multiple sclerosis (MS). We demonstrate neuronal antigens within CLN of MS patients. In monkeys and mice with experimental autoimmune encephalomyelitis (EAE) and in mouse models with non-inflammatory CNS damage, the type and extent of CNS damage was associated with the frequencies of CNS antigens within the cervical lymph nodes. In addition, CNS antigens drained to the spinal-cord-draining lumbar lymph nodes. In human MS CLN, neuronal antigens were present in pro-inflammatory antigen-presenting cells (APC), whereas the majority of myelin-containing cells were anti-inflammatory. This may reflect a different origin of the cells or different drainage mechanisms. Indeed, neuronal antigen-containing cells in human CLN did not express the lymph node homing receptor CCR7, whereas myelin antigen-containing cells in situ and in vitro did. Nevertheless, CLN from EAE-affected CCR7-deficient mice contained equal amounts of myelin and neuronal antigens as wild-type mice. We conclude that the type and frequencies of CNS antigens within the CLN are determined by the type and extent of CNS damage. Furthermore, the presence of myelin and neuronal antigens in functionally distinct APC populations within MS CLN suggests that differential immune responses can be evoked

Interdecadal North-Atlantic meridional overturning circulation variability in EC-EARTH

The Atlantic meridional overturning circulation (AMOC) in a 600 years pre-industrial run of the newly developed EC-EARTH model features marked interdecadal variability with a dominant time-scale of 50–60 years. An oscillation of approximately 2 Sverdrup (1 Sv = 106 m3 s?1) is identified, which manifests itself as a monopole causing the overturning to simultaneously strengthen (/weaken) and deepen (/shallow) as a whole. Eight years before the AMOC peaks, density in the Labrador-Irminger Sea region reaches a maximum, triggering deep water formation. This density change is caused by a counterclockwise advection of temperature and salinity anomalies at lower latitudes, which we relate to the north-south excursions of the subpolar-subtropical gyre boundary and variations in strength and position of the subpolar gyre and the North Atlantic Current. The AMOC fluctuations are not directly forced by the atmosphere, but occur in a delayed response of the ocean to forcing by the North Atlantic Oscillation, which initiates “intergyre”-gyre fluctuations. Associated with the AMOC is a 60-year sea surface temperature variability in the Atlantic, with a pattern and timescale showing similarities with the real-world Atlantic Multidecadal Variability. This good agreement with observations lends a certain degree of credibility that the mechanism that is described in this article could be seen as representative of the real climate system