title: CD4-dependent signaling is required for a late checkpoint during Th2 development associated with resistance to activation-induced cell death.
abstract: Previous studies have found that class II-restricted T cells from CD4-deficient mice reconstituted with a tail-less CD4 transgene have a specific defect in the development of Th2 effector cells; however, the reason for this defect was not clear. Following stimulation with a high potency peptide and exogenous IL-4, CD4-dependent signaling is required for optimal generation of a Th2 effector population. However, initial IL-4 and GATA-3 transcription is appropriately induced, suggesting that the initial stages of Th2 development are intact and independent of CD4 after priming with a strong agonist peptide. In addition to the defect in Th2 development, CD4 mutant T cells are also relatively resistant to activation-induced cell death (AICD). Furthermore, inhibition of AICD in wild-type T cells causes a defect in Th2 development similar to that seen in the CD4 mutant T cells. These data support the hypothesis that CD4-dependent signaling pathways regulate a distinct checkpoint in the expansion and commitment phase of Th2 development, which is related to dysregulation of AICD.
authors.affiliation: Department of Immunology, The George Washington University, Washington, DC 20037, USA.
authors.forename: Zohreh
authors.initials: Z
authors.lastname: Tatari-Calderone
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Brogdon
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Tinsley
authors.forename: Anahita
authors.initials: A
authors.lastname: Ramezani
authors.forename: David
authors.initials: D
authors.lastname: Leitenberg
mesh_terms: D000818:Animals; D017209:Apoptosis; D015704:CD4 Antigens / Q000502:physiology*; D002454:Cell Differentiation; D007371:Interferon-gamma / Q000502:physiology; D008213:Lymphocyte Activation; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D019948:Receptors, Interleukin-4 / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D018418:Th2 Cells / Q000276:immunology / Q000502:physiology*
chemical_list: D015704:CD4 Antigens; D011948:Receptors, Antigen, T-Cell; D019948:Receptors, Interleukin-4; D007371:Interferon-gamma