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Journal of Virology, May 2002, p. 4294-4303, Vol. 76, No. 9
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.9.4294-4303.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

NK T Cells Contribute to Expansion of CD8+ T Cells and Amplification of Antiviral Immune Responses to Respiratory Syncytial Virus

Teresa R. Johnson,1,2,3 Seokmann Hong,2 Luc Van Kaer,2 Yasuhiko Koezuka,4 and Barney S. Graham1,2,3*

Departments of Medicine,1 Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee,2 Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland,3 Pharmaceutical Research Laboratory, Kirin Brewery Co., Ltd., Takasaki-shi, Gunma, Japan4

Received 15 October 2001/ Accepted 4 February 2002

CD1d-deficient mice have normal numbers of T lymphocytes and natural killer cells but lack V{alpha}14+ natural killer T cells. Respiratory syncytial virus (RSV) immunopathogenesis was evaluated in 129xC57BL/6, C57BL/6, and BALB/c CD1d-/- mice. CD8+ T lymphocytes were reduced in CD1d-/- mice of all strains, as shown by cell surface staining and major histocompatibility complex class I tetramer analysis, and resulted in strain-specific alterations in illness, viral clearance, and gamma interferon (IFN-{gamma}) production. Transient activation of NK T cells in CD1d+/+ mice by {alpha}-GalCer resulted in reduced illness and delayed viral clearance. These data suggest that early IFN-{gamma} production and efficient induction of CD8+-T-cell responses during primary RSV infection require CD1d-dependent events. We also tested the ability of {alpha}-GalCer as an adjuvant to modulate the type 2 immune responses induced by RSV glycoprotein G or formalin-inactivated RSV immunization. However, immunized CD1-deficient or {alpha}-GalCer-treated wild-type mice did not exhibit diminished disease following RSV challenge. Rather, some disease parameters, including cytokine production, eosinophilia, and viral clearance, were increased. These findings indicate that CD1d-dependent NK T cells play a role in expansion of CD8+ T cells and amplification of antiviral responses to RSV.

* Corresponding author. Mailing address: Vaccine Research Center, NIAID, NIH, 40 Convent Dr. MSC 3017, Bldg. 40, Rm. 2504, Bethesda, MD 20892-3017. Phone: (301) 594-8468. Fax: (301) 480-2771. E-mail: bgraham{at}nih.gov.

Journal of Virology, May 2002, p. 4294-4303, Vol. 76, No. 9
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.9.4294-4303.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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