Expanding roles for CD4 ⁺ T cells in immunity to viruses

Key Points

• CD4 ⁺ T cells are orchestrators, regulators and direct effectors of antiviral immunity.

• Neutralizing antibodies provide protection against many viral pathogens, and CD4 ⁺ T cells can help B cells to generate stronger and longer-lived antibody responses.

• CD4 ⁺ T cells help antiviral CD8 ⁺ T cells in two main ways: they maximize CD8 ⁺ T cell population expansion during a primary immune response and also facilitate the generation of virus-specific memory CD8 ⁺ T cell populations.

• In addition to their helper functions, CD4 ⁺ T cells contribute directly to viral clearance. They secrete cytokines with antiviral activities and, in some circumstances, can eliminate infected cells through cytotoxic killing.

• Memory CD4 ⁺ T cells provide superior protection during re-infection with a virus. Compared with new effector CD4 ⁺ T cells, memory CD4 ⁺ T cells have enhanced helper and effector functions and can rapidly trigger innate immune defence mechanisms early in the infection.

Abstract

Immunity to viruses is typically associated with the development of cytotoxic CD8 ⁺ T cells. However, CD4 ⁺ T cells are also important for protection during viral infection. Here, the authors describe the various ways in which different CD4 ⁺T cell subsets can contribute to the antiviral immune response.

Abstract

Viral pathogens often induce strong effector CD4 ⁺ T cell responses that are best known for their ability to help B cell and CD8 ⁺ T cell responses. However, recent studies have uncovered additional roles for CD4 ⁺ T cells, some of which are independent of other lymphocytes, and have described previously unappreciated functions for memory CD4 ⁺ T cells in immunity to viruses. Here, we review the full range of antiviral functions of CD4 ⁺ T cells, discussing the activities of these cells in helping other lymphocytes and in inducing innate immune responses, as well as their direct antiviral roles. We suggest that all of these functions of CD4 ⁺ T cells are integrated to provide highly effective immune protection against viral pathogens.