Differential expression of T-cell adhesion molecules and LFA-1-dependent intercellular adhesion in HgCl2-induced autoimmunity and immune suppression.
Exposure of Brown Norway (BN) rats to HgCl2 induces Th2-mediated systemic autoimmunity. In contrast, in Lewis rats, HgCl2 induces immune suppression, mediated by CD8+ T cells. HgCl2 was previously found to enhance expression of LFA-1, ICAM-1 and CD134 (OX40) on T cells in BN rats. In the present study, T cells from Lewis rats were studied at day 4 after injection of HgCl2. CD8+ T lymphoblasts were significantly increased, which were predominantly CD45RC(hi), and which showed enhanced LFA-1 expression. Furthermore, CD4+CD45RC(hi) T cells showed increased numbers of ICAM-1+ cells, whereas expression of CD134 and CD26 was relatively decreased in CD4+ T lymphoblasts. Ex vivo experiments demonstrated that HgCl2-exposure of BN rats, but not of Lewis rats, significantly enhances PMA [phorbol 12-myristate 13-acetate]-induced lymphocyte aggregation, mediated by LFA-1 and ICAM-1. In conclusion, HgCl2-injected Lewis rats show early signs of T-lymphocyte activation, predominantly on CD8+ cells. Strain-dependent effects of HgCl2 on cell adhesion molecules and expression of CD134 may play an important role in development of either autoimmunity or immune suppression.
Roos
A
A
Department of Pathology, Academic Medical Center, University of Amsterdam, The Netherlands.
Claessen
N
N
Schilder-Tol
E J
EJ
Weening
J J
JJ
Aten
J
J
D000818:Animals; D015551:Autoimmunity / Q000187:drug effects* / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D007165:Immunosuppression Therapy; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D016169:Lymphocyte Function-Associated Antigen-1 / Q000096:biosynthesis / Q000276:immunology; D008627:Mercuric Chloride / Q000494:pharmacology*; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology*
D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1; D008627:Mercuric Chloride