Revealing the role of CD4(+) T cells in viral immunity

Abstract

Protective immunity to chronic and acute viral infection relies on both the innate and adaptive immune response. Although neutralizing antibody production by B cells and cytotoxic activity of CD8(+) T cells are well-accepted components of the adaptive immune response to viruses, identification of the specific role of CD4(+) T cells in protection has been more challenging to establish. Delineating the contribution of CD4(+) T cells has been complicated by their functional heterogeneity, breadth in antigen specificity, transient appearance in circulation, and sequestration in tissue sites of infection. In this minireview, we discuss recent progress in identifying the multiple roles of CD4(+) T cells in orchestrating and mediating the immune responses against viral pathogens. We highlight several recent reports, including one published in this issue, that have employed comprehensive and sophisticated approaches to provide new evidence for CD4(+) T cells as direct effectors in antiviral immunity.

Figure 1.

Many CD4 T cells expand in parallel in response to virus infection. Recent advances now allow a full and unbiased assessment of this initial CD4 T cell repertoire to viral pathogens, typically composed of many peptide specificities, indicated by different colored symbols. As CD4 T cells expand in response to infection, they differentiate into subsets that possess distinct effector functions, including cytolysis, help for antibody responses, and cytokine production (three examples of subsets from the same original CD4 T cell precursor are shown here in alternate depths of color). Some of these functional subsets may be enriched for particular epitope specificities and others may be sequestered in infected tissues. Identification of the CD4 T cell population that limits protective immunity requires robust and sophisticated assays to isolate, quantify, and distinguish virus-specific CD4 T cells.