title: The type of responder T-cell has a significant impact in a human in vitro suppression assay.
abstract: BACKGROUND
  In type 1 diabetes (T1D), a prototypic autoimmune disease, effector T cells destroy beta cells. Normally, CD4(+)CD25(+high), or natural regulatory T cells (Tregs), counter this assault. In autoimmunity, the failure to suppress CD4(+)CD25(low) T cells is important for disease development. However, both Treg dysfunction and hyperactive responder T-cell proliferation contribute to disease.
  
  
  RESULTS
  We investigated human CD4(+)CD25(low) T cells and compared them to CD4(+)CD25(-) T cells in otherwise equivalent in vitro proliferative conditions. We then asked whether these differences in suppression are exacerbated in T1D. In both single and co-culture with Tregs, the CD4(+)CD25(low) T cells divided more rapidly than CD4(+)CD25(-) T cells, which manifests as increased proliferation/reduced suppression. Time-course experiments showed that this difference could be explained by higher IL-2 production from CD4+CD25(low) compared to CD4+CD25- T cells. There was also a significant increase in CD4+CD25(low) T-cell proliferation compared to CD4+CD25- T cells during suppression assays from RO T1D and at-risk subjects (n = 28, p = 0.015 and p = 0.024 respectively).
  
  
  CONCLUSIONS
  The in vitro dual suppression assays proposed here could highlight the impaired sensitivity of certain responder T cells to the suppressive effect of Tregs in human autoimmune diseases.
authors.affiliation: Department of Pediatrics, Max McGee National Research Center for Juvenile Diabetes, Medical College and Children's Hospital of Wisconsin, Milwaukee, Wisconsin, United States of America.
authors.forename: Srikanta
authors.initials: S
authors.lastname: Jana
authors.forename: Hope
authors.initials: H
authors.lastname: Campbell
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Woodliff
authors.forename: Jill
authors.initials: J
authors.lastname: Waukau
authors.forename: Parthav
authors.initials: P
authors.lastname: Jailwala
authors.forename: Jugal
authors.initials: J
authors.lastname: Ghorai
authors.forename: Soumitra
authors.initials: S
authors.lastname: Ghosh
authors.forename: Sanja
authors.initials: S
authors.lastname: Glisic
mesh_terms: D001327:Autoimmune Diseases / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D002469:Cell Separation; D018920:Coculture Techniques; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D050417:Insulin-Secreting Cells / Q000276:immunology; D007376:Interleukin-2 / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000166:cytology; D012306:Risk; D013601:T-Lymphocytes / Q000166:cytology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology
chemical_list: D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit