title: Impaired Th2 subset development in the absence of CD4.
abstract: Prior studies in CD4-deficient mice established the capacity of T helper (Th) lineage cells to mature into Th1 cells. Unexpectedly, challenge of these mice with Nippostrongylus brasiliensis, a Th2-inducing stimulus, failed to result in the development of Th2 cells. Additional studies were performed using CD4+ or CD4-CD8- (double-negative) T cell receptor (TCR) transgenic T cells reactive to LACK antigen of Leishmania major. Double-negative T cells were unable to develop into Th2 cells in vivo, and, unlike CD4+ T cells, could not be primed for interleukin-4 production in vitro. Similarly, CD4+ TCR transgenic T cells primed on antigen-presenting cells expressing mutant MHC class II molecules unable to bind CD4 did not differentiate into Th2 cells. These data suggest that interactions between the TCR, MHC II-peptide complex and CD4 may be involved in Th2 development.
authors.affiliation: Department of Medicine, University of California, San Francisco, 94143, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Fowell
authors.forename: J
authors.initials: J
authors.lastname: Magram
authors.forename: C W
authors.initials: CW
authors.lastname: Turck
authors.forename: N
authors.initials: N
authors.lastname: Killeen
authors.forename: R M
authors.initials: RM
authors.lastname: Locksley
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000378:metabolism; D015704:CD4 Antigens / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D015847:Interleukin-4 / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009154:Mutation; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D019076:Transgenes / Q000276:immunology
chemical_list: D015704:CD4 Antigens; D000949:Histocompatibility Antigens Class II; D011948:Receptors, Antigen, T-Cell; D015847:Interleukin-4