TH2 activated cells prevent experimental autoimmune uveoretinitis, a TH1-dependent autoimmune disease.
Mercuric chloride (HgCl2) injections protect (Lewis x Brown-Norway) F1 (F1) rats against experimental autoimmune uveoretinitis (EAU) induced by immunization with the retinal S antigen (S-Ag); in contrast HgCl2-injected F1 rats develop EAU following transfer of lymph node (LN) cells from rats immunized with S-Ag alone. In the present study we demonstrate that the ability of LN cells from rats protected against EAU to transfer the disease into naive F1 rats was considerably reduced. These LN cells neither produced interleukin (IL)-2 nor (interferon (IFN)-gamma but exhibited mRNA for IL-4. In contrast, LN cells from diseased rats easily transferred EAU into naive F1 rats, produced significant IL-2 and IFN-gamma levels but barely exhibited mRNA for IL-4. Furthermore protected rats predominantly produced IgG1 anti-S-Ag antibodies, while diseased rats produced IgG2b anti-S-Ag antibodies and the increase in expression of MHC class II molecules on B cells was higher in protected rats than in diseased rats. These data suggest that (1) to exert a protective effect, HgCl2 must act at an early stage of differentiation of precursors of S-Ag specific T cells, and (2) this effect is related to the preferential activation of TH2 cells to the detriment of uveitogenic TH1 cells. Finally, these results indicate that activation of TH2 cells protect from a TH1-dependent autoimmune disease.
Saoudi
A
A
INSERM U28, Hôpital Broussais, Paris, France.
Kuhn
J
J
Huygen
K
K
de Kozak
Y
Y
Velu
T
T
Goldman
M
M
Druet
P
P
Bellon
B
B
D000818:Animals; D001327:Autoimmune Diseases / Q000517:prevention & control*; D001483:Base Sequence; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007132:Immunoglobulin Isotypes / Q000032:analysis; D016219:Immunotherapy, Adoptive; D008213:Lymphocyte Activation; D008297:Male; D008627:Mercuric Chloride; D008969:Molecular Sequence Data; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D012173:Retinitis / Q000517:prevention & control*; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology*; D014605:Uveitis / Q000517:prevention & control*
D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D007132:Immunoglobulin Isotypes; D008627:Mercuric Chloride