title: The development of CD4+ T effector cells during the type 2 immune response.
abstract: Multiple pathways may be involved in the development of interleukin 4 (IL-4) producing T helper (Th) cells and the associated type 2 immune response. Increasing evidence suggests that the strength of signals delivered to the T cell may favor the development of the type 2 response. In contrast, antigen-presenting cell- (APC) derived stimuli produced following pattern recognition receptor binding during the innate response promotes the development of interferon-gamma (IFN-gamma) producing cells and the associated type 1 immune response. In many cases, the balance between increased signaling strength and the innate response may determine whether the type 2 response develops. T cell receptor (TCR), CD4, and costimulatory molecule interactions may all contribute to signal strength, but the type 2 immune response may be particularly dependent on the availability of coreceptor and costimulatory molecule interactions. B7 ligand interactions are required for the development of the type 2 immune response and interaction of CD28 with either B7-1 or B7-2 can provide sufficient signals for its initiation. In B7-2-deficient mice, the initial type 2 immune response is intact, but the response is not sustained, suggesting that B7-2 is important at later stages of the type 2 immune response. The roles of CD28 and CTLA-4 during the type 2 response remain unclear. The type 2 response to infectious pathogens is pronounced in CD28-/- mice, suggesting that other costimulatory molecule interactions can substitute for CD28 for the development of IL-4 producing T cells and the associated type 2 immune response.
authors.affiliation: Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA. wgause@usuhs.mil
authors.forename: W C
authors.initials: WC
authors.lastname: Gause
authors.forename: M
authors.initials: M
authors.lastname: Ekkens
authors.forename: D
authors.initials: D
authors.lastname: Nguyen
authors.forename: V
authors.initials: V
authors.lastname: Mitro
authors.forename: Q
authors.initials: Q
authors.lastname: Liu
authors.forename: F D
authors.initials: FD
authors.lastname: Finkelman
authors.forename: R J
authors.initials: RJ
authors.lastname: Greenwald
authors.forename: J F
authors.initials: JF
authors.lastname: Urban
mesh_terms: D000069594:Abatacept; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000378:metabolism; D018122:B7-1 Antigen / Q000235:genetics / Q000378:metabolism*; D018106:CD28 Antigens / Q000235:genetics / Q000378:metabolism*; D060908:CTLA-4 Antigen; D018796:Immunoconjugates; D015847:Interleukin-4 / Q000096:biosynthesis*; D051379:Mice; D008817:Mice, Mutant Strains; D015398:Signal Transduction; D017206:Strongylida Infections / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D015847:Interleukin-4; D000069594:Abatacept