Lack of CD200 enhances pathological T cell responses during influenza infection.
Influenza virus infection can be accompanied by life-threatening immune pathology most likely due to excessive antiviral responses. Inhibitory immune receptors may restrain such overactive immune responses. To study the role of the inhibitory immune receptor CD200R and its ligand CD200 during influenza infection, we challenged wild-type and CD200(-/-) mice with influenza virus. We found that CD200(-/-) mice in comparison to wild-type controls when inoculated with influenza virus developed more severe disease, associated with increased lung infiltration and lung endothelium damage. CD200(-/-) mice did develop adequate adaptive immune responses and were able to control viral load, suggesting that the severe disease was caused by a lack of control of the immune response. Interestingly, development of disease was completely prevented by depletion of T cells before infection, despite dramatically increased viral load, indicating that T cells are essential for the development of disease symptoms. Our data show that lack of CD200-CD200R signaling increases immune pathology during influenza infection, which can be reduced by T cell depletion.
Rygiel
Tomasz P
TP
Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
Rijkers
Eva S K
ES
de Ruiter
Talitha
T
Stolte
Ellen H
EH
van der Valk
Martin
M
Rimmelzwaan
Guus F
GF
Boon
Louis
L
van Loon
Anton M
AM
Coenjaerts
Frank E
FE
Hoek
Robert M
RM
Tesselaar
Kiki
K
Meyaard
Linde
L
D000818:Animals; D015703:Antigens, CD / Q000235:genetics* / Q000276:immunology; D004727:Endothelium / Q000473:pathology / Q000821:virology; D009980:Influenza A virus; D008212:Lymphocyte Depletion; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D019562:Viral Load
D015703:Antigens, CD; C492346:CD200 receptor, mouse; D008562:Membrane Glycoproteins; C042739:antigens, CD200