Both CD4+ and CD8+ T cells are essential to induce experimental autoimmune myasthenia gravis.
CD4+ T cells have been shown to be crucial in the development of experimental autoimmune myasthenia gravis (EAMG). The role of CD8+ T cells in EAMG is less well established. We previously showed that antibody depletion of CD8+ T cells in rats effectively suppresses EAMG. To further study the role and relationship of CD4+ versus CD8+ T cells in induction of EAMG, CD4-/-, CD8-/-, and CD4-8- mutant C57BL/6 mice and the parent CD4+8- wild-type mice were immunized with Torpedo acetylcholine receptor (AChR) plus complete Freund's adjuvant. Clinical EAMG was nearly completely prevented in CD4-8-, CD4-/-, and CD8-/- mice. This was associated with strongly reduced AChR-specific T and B cell responses, and with reduced levels of AChR-reactive interferon gamma (IFN-gamma) and interleukin 4 (IL-4) mRNA-expressing cells in lymphoid organs when compared with CD4+8+ wild-type mice. We conclude that (a) both CD4+ and CD8+ T cells are essential for development of EAMG, and a collaboration between these cell types may be necessary; (b) CD4+ as well as CD8+ T cells secrete IFN-gamma and IL-4, and both cytokines are involved in the development of EAMG; and (c), besides T cells, other immune cells might also be responsible for help of anti-AChR antibody production.
Zhang
G X
GX
Division of Neurology, Huddinge Hospital, Stockholm, Sweden.
Xiao
B G
BG
Bakhiet
M
M
van der Meide
P
P
Wigzell
H
H
Link
H
H
Olsson
T
T
D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D015870:Gene Expression; D007371:Interferon-gamma / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009157:Myasthenia Gravis / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics; D011978:Receptors, Nicotinic / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer; D016212:Transforming Growth Factor beta / Q000235:genetics
D001323:Autoantibodies; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; D016212:Transforming Growth Factor beta; D015847:Interleukin-4; D007371:Interferon-gamma