Regulatory role of OX22high T cells in mercury-induced autoimmunity in the brown Norway rat.
The monoclonal antibody OX22 defines a functional split within CD4+ T cells in the rat, with OX22high cells mainly producing interleukin 2 (IL-2) and interferon gamma and responsible for delayed-type hypersensitivity responses, and OX22low cells mainly producing IL-4 and -5 and responsible for providing B cell help. There are reciprocal interactions between OX22high and OX22low cells, and it has been suggested that the OX22low subset has a role in the prevention of autoimmunity. We have used OX22 in vivo to define the role of these subsets in mercuric chloride-induced autoimmunity in the Brown Norway rat. In this model, there is polyclonal B cell activation and animals develop widespread tissue injury. Treatment of thymectomized animals with OX22 led to a profound reduction in the number of OX22high T cells in the peripheral blood. OX22-treated animals consistently developed more severe tissue injury than controls given an irrelevant antibody of the same isotype. Control animals pretreated with broad spectrum antimicrobial drugs showed milder tissue injury, but this protective effect of antimicrobials was lost in OX22-treated animals. Transfer of naive T cells to OX22-treated animals provided protection, but if T cells were depleted in vitro of OX22high cells before transfer, this effect was lost. These data provide evidence for a protective immunoregulatory role for OX22high T cells in mercuric chloride-induced autoimmunity.
Mathieson
P W
PW
Department of Medicine, University of Cambridge, UK.
Thiru
S
S
Oliveira
D B
DB
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D015551:Autoimmunity / Q000187:drug effects / Q000276:immunology*; D001485:Basement Membrane / Q000276:immunology; D001835:Body Weight; D005260:Female; D005434:Flow Cytometry; D007249:Inflammation / Q000139:chemically induced; D007678:Kidney Glomerulus / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D008627:Mercuric Chloride; D051381:Rats; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D000911:Antibodies, Monoclonal; D008627:Mercuric Chloride; D017493:Leukocyte Common Antigens