Lymphotoxin-alpha-deficient mice can clear a productive infection with murine gammaherpesvirus 68 but fail to develop splenomegaly or lymphocytosis.
Respiratory challenge with murine gammaherpesvirus 68 (MHV-68) leads to an acute productive infection of the lung and a persistent latent infection in B lymphocytes, epithelia, and macrophages. The virus also induces splenomegaly and an increase in the number of activated CD8 T cells in the circulation. Lymphotoxin- alpha-deficient (LTalpha(-/-)) mice have no lymph nodes and have disrupted splenic architecture. Surprisingly, in spite of the severe defect in secondary lymphoid tissue, LTalpha(-/-) mice could clear a productive MHV-68 infection, although with delayed kinetics compared to wild-type mice, and could control latent infection. Cytotoxic T-cell activity was comparable in the lungs and spleens of LTalpha(-/-) and wild-type mice. However, splenic gamma interferon responses were substantially reduced in LTalpha(-/-) mice. Furthermore, LTalpha(-/-) mice failed to develop splenomegaly or lymphocytosis. Although germinal centers were absent, LTalpha(-/-) mice were able to class switch and showed significant virus-specific antibody titers. This work demonstrates that organized secondary lymphoid tissue is not an absolute requirement for the generation of immune responses to viral infections.
Lee
B J
BJ
La Jolla Institute for Allergy and Immunology, San Diego, California 92121, USA.
Santee
S
S
Von Gesjen
S
S
Ware
C F
CF
Sarawar
S R
SR
D016475:3T3 Cells; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D005260:Female; D018142:Gammaherpesvirinae / Q000276:immunology* / Q000502:physiology; D006566:Herpesviridae Infections / Q000276:immunology* / Q000503:physiopathology; D017578:Immunoglobulin Class Switching; D007371:Interferon-gamma / Q000096:biosynthesis; D008168:Lung / Q000821:virology; D008218:Lymphocytosis / Q000276:immunology / Q000821:virology; D008233:Lymphotoxin-alpha / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011014:Pneumonia / Q000276:immunology / Q000503:physiopathology; D013163:Splenomegaly / Q000276:immunology / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014779:Virus Replication
D000914:Antibodies, Viral; D008233:Lymphotoxin-alpha; D007371:Interferon-gamma