Neonatal induction of tolerance to T(h)2-mediated autoimmunity in rats.
Brown-Norway (BN) rats are highly susceptible to drug-induced immune dysregulations and when injected with mercuric chloride (HgCl(2)) or sodium aurothiopropanolsulfonate (ATPS), they develop a syndrome characterized by a polyclonal B cell activation depending upon CD4(+) T(h)2 cells that recognize self-MHC class II molecules. Since peripheral tolerance of T(h)2 cells might be crucial in the prevention of immunological manifestations such as allergy, establishing conditions for inducing tolerance to HgCl(2)- or ATPS-mediated immune manifestations appeared to be of large interest. We report here that BN rats neonatally injected with HgCl(2): (i) do not develop the mercury disease, (ii) remain resistant to HgCl(2)-induced autoimmunity at 8 weeks of age and later, provided they are regularly exposed to HgCl(2), (iii) are still susceptible to ATPS-induced immune manifestations, and (iv) exhibit spleen cells that adoptively transfer tolerance to HgCl(2)-induced autoimmunity in naive, slightly irradiated, syngeneic recipients. These findings demonstrate that dominant specific tolerance can be neonatally induced using a chemical otherwise responsible for T(h)2-mediated autoimmunity.
Field
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INSERM U430 Hôpital Broussais, Pavillon Leriche, 96 rue Didot, 75674 Paris Cedex 14, France.
Caccavelli
L
L
Fillion
J
J
Kuhn
J
J
Mandet
C
C
Druet
P
P
Bellon
B
B
D019264:Adoptive Transfer; D000818:Animals; D000831:Animals, Newborn / Q000276:immunology*; D015551:Autoimmunity; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D004112:Dimercaprol / Q000031:analogs & derivatives / Q000633:toxicity; D007108:Immune Tolerance; D008627:Mercuric Chloride / Q000633:toxicity; D050607:Organogold Compounds; D009942:Organometallic Compounds / Q000633:toxicity; D020005:Propanols; D051381:Rats; D011914:Rats, Inbred BN; D013438:Sulfhydryl Compounds; D018418:Th2 Cells / Q000502:physiology*
D050607:Organogold Compounds; D009942:Organometallic Compounds; D020005:Propanols; D013438:Sulfhydryl Compounds; D004112:Dimercaprol; D008627:Mercuric Chloride; C013394:aurotioprol