TY - JOUR
T1 - Measles virus-induced immunosuppression in SLAM knock-in mice
AU - Koga, Ritsuko
AU - Ohno, Shinji
AU - Ikegame, Satoshi
AU - Yanagi, Yusuke
N1 - Funding Information:
Recently, there has been considerable interest in the decay D + --'11' n + ~1 due to conflicting measurements of the branching ratio relative to the decay D~--. 0n + \[1 -4\]. A precise measurement of this decay rate is of interest since a large D~+ -,q'n + branching ratio poses problems for current models, which predict values of BR(D~ + ~'n +)/BR(D + ~0n +) of less than 2 \[5 ,6 \]. Among the mechanisms offered as possible explanations for larger values are final-state interactions and even the presence of a nearby scalar resonance \[5 ,7 \]. Several experiments have searched for evidence of the decay D~+ ~l\]'n +. An indication for a signal was reported by Mark II \[1 \], with a value of 4.8 + 2.1 for the ratio BR(D + --,Tl'n +)/BR(D + --.0n +). Subsequently, NA14' also claimed evidence for this channel, with a value of 5.0 + 1.8 + 1.2 for the same ratio \[3\]. However, in considerable disagreement with these results are the upper limits reported by Mark III and E691. These experiments have determined BR(D + ~l\]'n + )/BR(D + ~0n + ) to be less than 1.9 \[2\] and less than 1.7 \[4\] respectively, both at the t Supported by the German Bundesministerium f'tir Forschung und Technologie, under contract number 054DO51P. 2 Supported by the German Bundesministerium f'tir Forschung und Technologie, under contract number 054ER 12P. 3 Supported by the German Bundesministerium f'tir Forschung und Technologie, under contract number 054HD24P. 4 McGill University, Montreal, Quebec, Canada H3C 3J7. 5 University of Toronto, Toronto, Ontario, Canada M5S IA7. 6 Carleton University, Ottawa, Ontario, Canada K1S 5B6. 7 Supported by the Natural Sciences and Engineering Research Council, Canada. 8 Supported by the German Bundesministerium f'dr Forschung und Technologie, under contract number 054KA 17P. 9 Supported by Alexander yon Humboldt Stiftung, Bonn, FRG. 1o Supported by Raziskovalna skupnost Slovenije and the Inter-nationales Biiro KfA, Jiilich. 11 Supported by the Swedish Research Council. 12 Supported by the US Department of Energy, under contract DE-AS09-80ER 10690. at References in this paper to a specific charged state are to be interpreted as implying the charge-conjugate state also.
PY - 2010/5
Y1 - 2010/5
N2 - 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.
AB - 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.
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U2 - 10.1128/JVI.02525-09
DO - 10.1128/JVI.02525-09
M3 - Article
C2 - 20200244
AN - SCOPUS:77951461118
VL - 84
SP - 5360
EP - 5367
JO - Journal of Virology
JF - Journal of Virology
SN - 0022-538X
IS - 10
ER -