Qualitative and Quantitative Requirements for CD4+ T Cell-Mediated Antiviral Protection

• Published in: The Journal of immunology (1950) 1999-03, Vol.162 (5), p.2867-2874
• Main Authors: Maloy, Kevin J, Burkhart, Christoph, Freer, Giulia, Rulicke, Thomas, Pircher, Hanspeter, Kono, Dwight H, Theofilopoulos, Argyrios N, Ludewig, Burkhard, Hoffmann-Rohrer, Urs, Zinkernagel, Rolf M, Hengartner, Hans
• Format: Article
• Language: English
• Subjects: Adoptive Transfer; Animals; Antibodies, Viral - blood; CD4-Positive T-Lymphocytes - immunology; Female; Immunoglobulin Class Switching; Immunoglobulin G - blood; Membrane Glycoproteins; Mice; Mice, Inbred C57BL; Mice, Transgenic; Receptors, Antigen, T-Cell, alpha-beta - physiology; Vesicular stomatitis Indiana virus - immunology; Viral Envelope Proteins - immunology; Virus Diseases - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.162.5.2867

CD4+ Th cells deliver the cognate and cytokine signals that promote the production of protective virus-neutralizing IgG by specific B cells and are also able to mediate direct antiviral effector functions. To quantitatively and qualitatively analyze the antiviral functions of CD4+ Th cells, we generated transgenic mice (tg7) expressing an MHC class II (I-Ab)-restricted TCR specific for a peptide derived from the glycoprotein (G) of vesicular stomatitis virus (VSV). The elevated precursor frequency of naive VSV-specific Th cells in tg7 mice led to a markedly accelerated and enhanced class switching to virus-neutralizing IgG after immunization with inactivated VSV. Furthermore, in contrast to nontransgenic controls, tg7 mice rapidly cleared a recombinant vaccinia virus expressing the VSV-G (Vacc-IND-G) from peripheral organs. By adoptive transfer of naive tg7 CD4+ T cells into T cell-deficient recipients, we found that 105 transferred CD4+ T cells were sufficient to induce isotype switching after challenge with a suboptimal dose of inactivated VSV. In contrast, naive transgenic CD4+ T cells were unable to adoptively confer protection against peripheral infection with Vacc-IND-G. However, tg7 CD4+ T cells that had been primed in vitro with VSV-G peptide were able to adoptively transfer protection against Vacc-IND-G. These results demonstrate that the antiviral properties of CD4+ T cells are governed by the differentiation status of the CD4+ T cell and by the type of effector response required for virus elimination.