title: Measles virus-induced immunosuppression in SLAM knock-in mice.
abstract: Measles virus (MV) causes transient severe immunosuppression in patients, which may lead to secondary viral and bacterial infections, largely accounting for measles-related morbidity and mortality. MV is known to infect immune cells by using the human signaling lymphocyte activation molecule (SLAM; also called CD150) as a cellular receptor, but the mechanism by which MV causes immunosuppression is not well understood. We show that MV infection of SLAM knock-in mice, in which the V domain of mouse SLAM was replaced by the V domain of human SLAM, crossed with alpha/beta-interferon receptor knockout mice, reproduced many immunological alterations observed in human patients. These included lymphopenia, inhibition of T-cell proliferation and antibody production, increased production of the Th2 cytokine interleukin-4 (IL-4) and the immunosuppressive cytokine IL-10, and suppression of contact hypersensitivity. Gross redistribution of lymphocytes among lymphoid tissues was not apparent in infected mice, nor was an increase of regulatory T cells. The numbers of lymphocytes in lymph nodes remained almost unchanged after MV infection, despite enhanced apoptosis, suggesting that lymph nodes were replenished with lymphocytes from the peripheral blood, which may have contributed to the observed lymphopenia in the spleen. Blocking of IL-10 by use of an anti-IL-10 receptor antibody ameliorated suppression of contact hypersensitivity in infected mice. These results indicate that SLAM knock-in mice lacking the expression of the alpha/beta-interferon receptor serve as a useful small animal model with which to elucidate MV-induced immunosuppression.
authors.affiliation: Department of Virology, Faculty of Medicine, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Koga
authors.forename: Shinji
authors.initials: S
authors.lastname: Ohno
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ikegame
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Yanagi
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D004195:Disease Models, Animal; D055879:Gene Knock-In Techniques; D006801:Humans; D007108:Immune Tolerance; D008198:Lymph Nodes / Q000276:immunology; D008231:Lymphopenia; D008459:Measles virus / Q000276:immunology* / Q000472:pathogenicity*; D051379:Mice; D018345:Mice, Knockout; D053633:Receptor, Interferon alpha-beta / Q000172:deficiency; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D011991:Receptors, Virus / Q000235:genetics / Q000502:physiology*; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D013154:Spleen / Q000276:immunology; D019076:Transgenes
chemical_list: D015703:Antigens, CD; D011956:Receptors, Cell Surface; D011991:Receptors, Virus; C000604059:SLAMF1 protein, human; D053633:Receptor, Interferon alpha-beta; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1