Cytotoxic CD4 T cells in antiviral immunity

Abstract

CD4 T cells that acquire cytotoxic phenotype and function have been repeatedly identified in humans, mice, and other species in response to many diverse pathogens. Since CD4 cytotoxic T cells are able to recognize antigenic determinants unique from those recognized by the parallel CD8 cytotoxic T cells, they can potentially contribute additional immune surveillance and direct effector function by lysing infected or malignant cells. Here, we briefly review much of what is known about the generation of cytotoxic CD4 T cells and describe our current understanding of their role in antiviral immunity. Furthering our understanding of the many roles of CD4 T cells during an anti-viral response is important for developing effective vaccine strategies that promote long-lasting protective immunity.

Figure 1

The many roles of CD4 T cells in promoting antiviral immunity multiple direct and indirect cellular interactions with CD4 T cells promotes antiviral immunity. CD4 T cells can promote affinity maturation and antibody class switching by B cells, enhance antigen presentation and costimulation of dendritic cells (DC), induce the phagocytic activity of macrophages, and promote the development of CD8 T cells into cytotoxic T lymphocytes (CTLs) and functional memory cells. A lesser known role for CD4 T cells is the development of cytotoxic activity directed against infected target cells.

Figure 2

CD4 T cell effector subsets A CD4 T cell (Th) can differentiate into unique effector subsets determined in part by the cytokine milieu that is present when the cell encounters antigen. Effector subsets are classified by the dominant transcription factor in concert with the cytokines that they express. Th cells that develop optimal cytotoxic activity (ThCTL) may be distinct from the other identified effector subtypes.