Neuroantigen-specific Th2 cells are inefficient suppressors of experimental autoimmune encephalomyelitis induced by effector Th1 cells.
We have identified a method of polarizing polyclonal populations of activated T helper cells toward either the Th1 or Th2 phenotype using different short-term in vitro culture conditions. Since the Ag used was an encephalitogenic peptide for SJL/J mice, the pathogenic potential of these cell populations was tested in an adoptive transfer model of experimental autoimmune encephalomyelitis (EAE). Th1 cells reproducibly caused severe EAE, whereas highly polarized Th2 cells did not. Furthermore, highly polarized Th2 cells did not suppress EAE caused by Th1 cells. The anti-inflammatory cytokines made by Th2 cells may simply fail to inhibit tissue destruction mediated by differentiated Th1 cells at the effector phase of the disease. It is also possible that highly polarized Th2 cells may be inefficient at crossing the blood-brain barrier, which may limit their suppressive potential. In contrast, incompletely skewed T cell populations that produced high levels of both Th1 and Th2 cytokines were consistently only weakly encephalitogenic. Therefore, disease inhibition by Th2 cytokines may best be accomplished by intervention at earlier points preceding development of differentiated Th1 cells.
Khoruts
A
A
University of Minnesota Medical School, Department of Microbiology, Minneapolis 55455.
Miller
S D
SD
Jenkins
M K
MK
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D002490:Central Nervous System / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005260:Female; D007165:Immunosuppression Therapy; D007167:Immunotherapy; D051379:Mice; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*