Functional Analysis of CD28/B7 and CD40/CD40L Costimulation During the in vivo Type 2 Immune Response.

摘要

Cytokine production and other effector functions of CD4+ T helper (Th) cells are crucial for the initiation of a primary immune response. The activation of naive CD4+ Th cells requires two signals delivered from antigen presenting cells (APCs). The engagement of the T cell surface receptor (TCR) by antigenic peptides presented in the context of major histocompatibility complex (MHC) class H molecules on APCs provides the primary signal, but this Ag- specific signal alone is not sufficient to activate naive CD4+ Th cells. A second or costimnulatory signal from ApCs, which is independent of T cell receptor signaling, is required for optimal activation, proliferation, and cytokine production by naive CD4+ Th cells. Recent studies have shown that T cell surface molecule CD28, and its homologue CTLA-4, can provide costimulatory signals to Th cells when they interact with their ligands, B7-1/B7-2 on APCs. Interactions between Th cell surface CD40 ligand (CD4OL) and B cell CD40 molecules have also been shown to costimulate Th cell activation. In this investigation, the role of CD28/CTLA4-ligand costimulation in naive Th cell activation and T cell cytokine production was examined by blocking CTLA-4 ligand interactions in two in vivo type 2 immune response models. These studies demonstrated that costimulation through CD28/ CTLA4 is required for Th cell priming leading to IL-4 cytokine production, B cell activation, and IgE secretion during an in vivo type 2 mucosal immune response to a nematode parasite.