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Journal of Virology, March 2000, p. 2786-2792, Vol. 74, No. 6
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Lymphotoxin-alpha -Deficient Mice Can Clear a Productive Infection with Murine Gammaherpesvirus 68 but Fail To Develop Splenomegaly or Lymphocytosisdagger

Bong Joo Lee, Sybil Santee, Sigrid Von Gesjen, Carl F. Ware, and Sally R. Sarawar*

La Jolla Institute for Allergy and Immunology, San Diego, California 92121

Received 5 August 1999/Accepted 2 December 1999

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.

* Corresponding author. Mailing address: Division of Molecular Immunology, La Jolla Institute for Allergy and Immunology, 10355 Science Center Dr., San Diego, CA 92121. Phone: (858) 678-4661. Fax: (619) 558-3526. E-mail: ssarawar{at}liai.org.

dagger Manuscript no. 314 from the La Jolla Institute for Allergy and Immunology.

Journal of Virology, March 2000, p. 2786-2792, Vol. 74, No. 6
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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