Enhanced T lymphocyte expression of LFA-1, ICAM-1, and the TNF receptor family member OX40 in HgCl2-induced systemic autoimmunity.
Injection of mercuric chloride into Brown Norway (BN) rats induces a T lymphocyte-dependent autoimmune syndrome. In order to investigate whether modification of adhesion and costimulatory molecules on T lymphocytes may be involved in early T lymphocyte activation by HgCl2, the authors analysed expression of these molecules in peripheral lymph node cells from BN rats at day 4 after injection of HgCl2. Tri-colour flow cytometry was performed for expression analysis within CD45RC-defined subsets of CD4+ and CD8+ cells. Compared to control rats, HgCl2-exposed rats showed increased numbers of lymphocytes, especially of T lymphocyte blast cells. The levels of LFA-1 expression as well as the fractions of ICAM-1 + cells were significantly increased in all CD45RC-defined subsets of CD4+ and CD8+ cells. Within the CD4 + CD45RC10 T lymphocyte population, HgCl2-injected rats showed a highly significant increase in the number of cells expressing OX40, which is a member of the TNF receptor family. Moreover, only CD4 + CD45RC10 blast cells of HgCl2-exposed rats showed decreased expression of CD43, increased expression of CD49d and decreased numbers of CD26 + cells. The results indicate that induction of autoimmunity by HgCl2 in BN rats is associated with altered expression of T lymphocyte costimulatory molecules, predominantly on CD4+ CD45RC10 cells, which may be caused by a direct effect of HgCl2 on these cells, and may precipitate further activation of T and B lymphocytes by HgCl2.
Roos
A
A
Department of Pathology, University of Amsterdam, The Netherlands.
Claessen
N
N
Weening
J J
JJ
Aten
J
J
D000818:Animals; D015551:Autoimmunity / Q000187:drug effects*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D017493:Leukocyte Common Antigens / Q000096:biosynthesis / Q000235:genetics; D008213:Lymphocyte Activation / Q000187:drug effects; D016169:Lymphocyte Function-Associated Antigen-1 / Q000096:biosynthesis*; D008627:Mercuric Chloride / Q000494:pharmacology*; D010641:Phenotype; D051381:Rats; D011914:Rats, Inbred BN; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000737:chemistry* / Q000276:immunology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000096:biosynthesis*
D016169:Lymphocyte Function-Associated Antigen-1; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; C505718:Tnfrsf4 protein, rat; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D018799:Intercellular Adhesion Molecule-1; D008627:Mercuric Chloride; D017493:Leukocyte Common Antigens