Publication

Qualitative and quantitative requirements for CD4+ T cell-mediated antiviral protection

Journal Paper/Review - Mar 1, 1999

Units
PubMed

Citation
Maloy K, Zinkernagel R, Hoffmann-Rohrer U, Ludewig B, Theofilopoulos A, Kono D, Pircher H, Rülicke T, Freer G, Burkhart C, Hengartner H. Qualitative and quantitative requirements for CD4+ T cell-mediated antiviral protection. Journal of immunology (Baltimore, Md. : 1950) 1999; 162:2867-74.
Type
Journal Paper/Review (English)
Journal
Journal of immunology (Baltimore, Md. : 1950) 1999; 162
Publication Date
Mar 1, 1999
Issn Print
0022-1767
Pages
2867-74
Brief description/objective

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.