title: T cell sensitivity to TGF-beta is required for the effector function but not the generation of splenic CD8+ regulatory T cells induced via the injection of antigen into the anterior chamber.
abstract: The introduction of antigen into the anterior chamber (AC) of the eye induces the production of antigen-specific splenic CD8(+) regulatory T cells (AC-SPL cells) that suppress a delayed-type hypersensitivity (DTH) reaction in immunized mice. Because the generation of these regulatory T cells is also induced by exposure to transforming growth factor (TGF)-beta and antigen or F4/80(+) cells exposed to TGF-beta and antigen in vitro, we investigated (i) whether these cells are produced in dominant negative receptor for transforming growth factor beta receptor type II (dnTGFbetaRII) or Cbl-b(-/-) mice whose T cells are resistant to TGF-beta, (ii) whether DTH is suppressed by wild type (WT) CD8(+) AC-SPL cells in Cbl-b(-/-) and dnTGFbetaRII mice and (iii) the effect of antibodies to TGF-beta on the suppression of DTH by CD8(+) AC-SPL cells. DnTGFbetaRII immunized and Cbl-b(-/-) mice produced splenic CD8(+) regulatory cells after the intracameral injection of antigen and immunization. The suppression of a DTH reaction by CD8(+) AC-SPL cells in WT mice was blocked by the local inclusion of antibodies to TGF-beta when WT splenic CD8(+) AC-SPL cells were injected into the DTH reaction site. Moreover, the DTH reaction in immunized dnTGFbetaRII and Cbl-b(-/-) mice was not suppressed by the transfer of WT CD8(+) AC-SPL cells to the site challenged with antigen. In aggregate, these observations suggest that T cell sensitivity to TGF-beta is not an obligate requirement for the in vivo induction of CD8(+) AC-SPL T cells but the suppression of an in vivo DTH reaction by CD8(+) AC-SPL cells is dependent on TGF-beta.
authors.affiliation: Department of Immunology, University of Connecticut Health Center, Farmington, CT 06030-3105, USA. cone@uchc.edu
authors.forename: Robert E
authors.initials: RE
authors.lastname: Cone
authors.forename: Subhasis
authors.initials: S
authors.lastname: Chattopadhyay
authors.forename: Roshanak
authors.initials: R
authors.lastname: Sharafieh
authors.forename: Yen
authors.initials: Y
authors.lastname: Lemire
authors.forename: James
authors.initials: J
authors.lastname: O'Rourke
authors.forename: Richard A
authors.initials: RA
authors.lastname: Flavell
authors.forename: Robert B
authors.initials: RB
authors.lastname: Clark