title: Analysis of in vivo regulatory properties of T cells activated in vitro by TGFbeta2-treated antigen presenting cells.
abstract: OBJECTIVE
  To determine whether naive T cells activated in vitro by antigen-pulsed, transforming growth factor(beta) (TGFbeta)-treated antigen presenting cells (APCs) acquire the capacity to suppress the induction and expression of delayed hypersensitivity in vivo.
  
  
  METHODS
  Naive ovalbumin (OVA)specific T cells from DO 11.10 Tcr transgenic mice were stimulated in vitro with OVA-pulsed TGF(beta2)-treated APCs. The cultured cells were harvested and assayed for in vitro production of mature TGFbeta. Similar cells were coinjected with primed OVA-specific BALB/c T cells plus OVA-pulsed APCs into ear pinnae of normal BALB/c mice (assay for delayed hypersensitivity expression) or coinjected with OVA-pulsed APCs into footpads of naive DO11.10 mice whose draining lymph node cells were harvested 4 days later and assayed in vitro for capacity to secrete interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) when stimulated with OVA (assay for induction of delayed hypersensitivity).
  
  
  RESULTS
  DO11.10 T cells activated in vitro by OVA-pulsed TGFbeta2-treated APCs secreted large amounts of mature TGFbeta and suppressed the expression of delayed hypersensitivity in a local adoptive transfer assay. Suppression was reversed in the presence of neutralizing anti-TGFbeta antibodies. In addition, in vitro generated regulatory T cells influenced naive T cells in DO11.10 mice that were responding to an initial immunization with OVA to secrete IL-4, rather than IFN-gamma. This influence was independent of TGFbeta.
  
  
  CONCLUSIONS
  OVA-pulsed APCs, pretreated in vitro with TGF(beta)2, activate DO11.10 T cells in a manner that endows the responding cells with the capacity to suppress the induction and then the expression of delayed hypersensitivity in vivo. In certain ways, these properties of in vitro-activated DO11.10 T cells resemble the properties of afferent and efferent regulatory T cells typically found in the spleens of animals with anterior chamber-associated immune deviation.
authors.affiliation: Department of Ophthalmology, Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: T
authors.initials: T
authors.lastname: Kezuka
authors.forename: J W
authors.initials: JW
authors.lastname: Streilein
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects*; D002478:Cells, Cultured; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology / Q000517:prevention & control; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000528:radiation effects; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000494:pharmacology*
chemical_list: D016212:Transforming Growth Factor beta; D015847:Interleukin-4; D007371:Interferon-gamma; D010047:Ovalbumin