Treg and T-effector cells in autoimmune CNS inflammation: a delicate balance, easily disturbed.
EAE is the primary pre-clinical disease for modelling the autoimmune/inflammatory component of multiple sclerosis. In fact, EAE is the primordial CD4(+) T-cell-driven autoimmune disease model. It is striking (although perhaps unsurprising) that more than 10 000 publications over seven decades have provided a confusing, rather than a satisfying, picture of etiopathology. In the current issue of the European Journal of Immunology, an analysis of mice lacking LFA-1 is reported. Given the role of this integrin in T-cell activation and effector cell migration, one might predict resistance of LFA-1(-/-) mice to EAE induction. Instead, this study unexpectedly reports that EAE was exacerbated in the absence of LFA-1, and that this correlated with a decrease in the steady-state numbers of Foxp3(+) Treg in the LFA-1(-/-) mice. Previous studies on the role of LFA-1 in EAE have been reviewed recently. This Commentary focuses on our current understanding of Treg function in the development and resolution of EAE and discusses how the absence of LFA-1 might unhinge these, possibly by altering the generation of Treg in the thymus, their expansion in response to autoantigen immunization, or their infiltration of the CNS.
Medical Research Council/University of Edinburgh Centre for Inflammation Research, Centre for Multiple Sclerosis Research, Queen's Medical Research Institute, Edinburgh, UK. steve.anderton@ed.ac.uk
Stephen M
SM
Anderton
D000818:Animals; D015551:Autoimmunity; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002490:Central Nervous System / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D006706:Homeostasis / Q000235:genetics / Q000276:immunology; D007249:Inflammation; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D016169:Lymphocyte Function-Associated Antigen-1