Role of Ox40 Signals in Coordinating Cd4 T Cell Selection, Migration, and Cytokine Differentiation in T Helper (Th)1 and Th2 Cells

Our survival depends on our ability to clonally expand rare CD4 lymphocytes and instruct them to help effector cells. Two very different types of CD4 T cell response are required for protective immunity. Immunity to intracellular infections like tuberculosis is dependent on priming and expanding inflammatory IFN-γ–expressing CD4 T cells that acquire the capability to migrate out into the tissue and activate macrophages to kill infected cells. In contrast, immunity to the exotoxin produced by diphtheria requires CD4 T cells to be primed to migrate into B follicles to foster germinal center (GC) development and the rapid production of high-affinity neutralizing antibodies. Although the outcomes of these two types of CD4 response are different, they have the same three components: (a) Identification and expansion of antigen-specific CD4 T cells; (b) instruction to secrete the appropriate cytokines; and (c) instruction...