The regulation of autoimmunity through CD4+ T cells.
Our experiments imply that it is possible to use monoclonal antibody therapy to reestablish self tolerance to self antigens. This can be achieved by using a short course of an nd anti-CD4 antibody thus avoiding the problem of long term immunosuppression. The mechanism by which such a state of self tolerance is achieved remains to be clarified but possible mechanisms include deletion or anergy of autoreactive T cells or some form of suppression mediated through local cytokine production. As this antibody induced state of tolerance can be reversed in the NOD mouse by cyclophospamide deletion cannot be the method by which autoreactivity is prevented. The mixing experiments which have been described in the thyroiditis experiments strongly suggest that anery is not the mechanism. It therefore remains most likely that tolerance induced following administration of nd anti-CD4 is an active process maintained through the production of an inhibitory cytokine. This ability to reprogram the immune system using monoclonal antibodies makes it not beyond the realms of possibility that individuals suffering from IDDM may become tolerant of their beta cell antigens and thus be able to regenerate their own beta cell mass. If this could indeed occur it might mean that a lifetime of insulin injections and the development of the life threatening complications that may accompany a disease like IDDM may be avoided.
Hutchings
P
P
Department of Pathology, University of Cambridge, UK.
Parish
N
N
O'Reilly
L
L
Dawe
K
K
Roitt
I M
IM
Cooke
A
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology* / Q000628:therapy; D015551:Autoimmunity / Q000502:physiology; D015704:CD4 Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003520:Cyclophosphamide / Q000494:pharmacology / Q000633:toxicity; D003921:Diabetes Mellitus, Experimental / Q000276:immunology* / Q000628:therapy; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000628:therapy; D005260:Female; D007167:Immunotherapy; D016219:Immunotherapy, Adoptive; D007515:Islets of Langerhans / Q000276:immunology; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD / Q000276:immunology*; D011828:Radiation Chimera / Q000276:immunology; D017634:Self Tolerance / Q000187:drug effects; D012737:Sex Factors; D013967:Thyroiditis, Autoimmune / Q000276:immunology
D000911:Antibodies, Monoclonal; D001324:Autoantigens; D015704:CD4 Antigens; D003520:Cyclophosphamide