Administration of anti-IFN-gamma antibody to beta 2-microglobulin-deficient mice delays influenza virus clearance but does not switch the response to a T helper cell 2 phenotype.
Treatment of mice that were homozygous for a beta 2-microglobulin gene disruption with a mAb that was specific for IFN-gamma delayed clearance of an influenza A virus from the respiratory tract for at least 3 days, whereas administration of an anti-IL-4 mAb had no effect. However, all mice survived and eventually cleared the virus. The anti-IFN-gamma significantly decreased both the level of class II MHC glycoprotein expression and the numbers of CD4+ lymphocytes in the inflammatory populations recovered by bronchoalveolar lavage of the pneumonic lung, whereas the total cell counts remained the same. These differences were not apparent for the regional mediastinal lymph nodes, although the frequency of lymph node B cells producing virus-specific Ab of the IgG2a subclass was greatly reduced. However, neither the anti-IFN-gamma nor anti-IL-4 treatments drastically altered the cytokine production profiles detected for freshly isolated lymphocytes by the using single cell ELISPOT assay or by ELISA of culture supernatants after in vitro restimulation with virus. Thus, neutralization of secreted IFN-gamma during the course of an influenza-specific response in beta 2-microglobulin-deficient mice that lack CD8+ T cells delays virus clearance and modifies the character of the host response, but does not cause the CD4+ subset to switch to a Th2 cytokine profile.
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105.
S R
SR
Sarawar
M
M
Sangster
R L
RL
Coffman
P C
PC
Doherty
D000818:Animals; D005260:Female; D007249:Inflammation / Q000276:immunology; D009980:Influenza A virus / Q000276:immunology; D007371:Interferon-gamma / Q000502:physiology*; D016753:Interleukin-10 / Q000502:physiology; D015847:Interleukin-4 / Q000502:physiology; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D001613:beta 2-Microglobulin / Q000172:deficiency*
D001613:beta 2-Microglobulin; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma