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Journal of Virology, October 1998, p. 8281-8288, Vol. 72, No. 10
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Long-Term CD4 Th1 and Th2 Memory following Acute Lymphocytic Choriomeningitis Virus Infection

Jason K. Whitmire,1 Mary S. Asano,2 Kaja Murali-Krishna,1 M. Suresh,1 and Rafi Ahmed1,*

Emory Vaccine Center and Department of Microbiology & Immunology, Emory University School of Medicine, Atlanta, Georgia 30322,1 and Department of Microbiology and Immunology, UCLA School of Medicine, Los Angeles, California 900242

Received 2 March 1998/Accepted 23 June 1998

CD4 T cells play a central role in viral immunity. They provide help for B cells and CD8 T cells and can act as effectors themselves. Despite their importance, relatively little is known about the magnitude and duration of virus-specific CD4 T-cell responses. In particular, it is not known whether both CD4 Th1 memory and CD4 Th2 memory can be induced by viral infections. To address these issues, we quantitated virus-specific CD4 Th1 (interleukin 2 [IL-2] and gamma-interferon) and Th2 (IL-4) responses in mice acutely infected with lymphocytic choriomeningitis virus (LCMV). Using two sensitive assays (enzyme-linked immunospot assay and intracellular stain) to measure cytokine production at the single-cell level, we found that both CD4 Th1 and Th2 responses were induced during primary LCMV infection. At the peak (day 8) of the response, the frequency of LCMV-specific CD4 Th1 cells was 1/35 to 1/160 CD4 T cells, and the frequency of Th2 cells was 1/400. After viral clearance, the numbers of virus-specific CD4 T cells dropped to 1/260 to 1/3,700 and then were maintained at this level indefinitely. Upon rechallenge with LCMV, both CD4 Th1 and Th2 memory cells made an anamnestic response in vivo. These results show that unlike some microbial infections in which only Th1 or Th2 responses are seen, an acute viral infection can induce a mixed CD4 T-cell response with long-term memory.

* Corresponding author. Mailing address: Emory Vaccine Center, Emory University School of Medicine, G211 Rollins Research Building, 1510 Clifton Rd., Atlanta, GA 30322. Phone: (404) 727-3571. Fax: (404) 727-3722. E-mail: ra{at}microbio.emory.edu.

Journal of Virology, October 1998, p. 8281-8288, Vol. 72, No. 10
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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Copyright © 1998 by the American Society for Microbiology. All rights reserved.