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Journal of Virology, May 2005, p. 5943-5951, Vol. 79, No. 10
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.10.5943-5951.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Roles of CD4⁺ T-Cell-Independent and -Dependent Antibody Responses in the Control of Influenza Virus Infection: Evidence for Noncognate CD4⁺ T-Cell Activities That Enhance the Therapeutic Activity of Antiviral Antibodies

Immunology Program, The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104-4268

Received 18 October 2004/ Accepted 11 January 2005

Previous studies have indicated that B cells make a significant contribution to the resolution of influenza virus infection. To determine how B cells participate in the control of the infection, we transferred intact, major histocompatibility complex class II (MHC-II)-negative or B-cell receptor (BCR)-transgenic spleen cells into B-cell-deficient and CD8⁺ T-cell-depleted µMT mice, termed µMT(–8), and tested them for ability to recover from infection. µMT(–8) mice that received no spleen cells invariably succumbed to the infection within 20 days, indicating that CD4⁺ T-cell activities had no significant therapeutic activity on their own; in fact, they were harmful and decreased survival time. Interestingly, however, they became beneficial in the presence of antiviral antibody (Ab). Injection of MHC-II^(–/–) spleen cells, which can provide CD4⁺ T-cell-independent (TI) but not T-cell-dependent (TD) activities, delayed mortality but only rarely resulted in clearance of the infection. By contrast, 80% of µMT(–8) mice injected with normal spleen cells survived and resolved the infection. Transfer of BCR-transgenic spleen cells, which contained 10 times fewer virus-specific precursor B cells than normal spleen cells, had no significant impact on the course of the infection. Taken together, the results suggest that B cells contribute to the control of the infection mainly through production of virus-specific Abs and that the TD Ab response is therapeutically more effective than the TI response. In addition, CD4⁺ T cells appear to contribute, apart from promoting the TD Ab response, by improving the therapeutic activity of Ab-mediated effector mechanisms.

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