title: Thyroid associated ophthalmopathy: evidence for CD4(+) gammadelta T cells; de novo differentiation of RFD7(+) macrophages, but not of RFD1(+) dendritic cells; and loss of gammadelta and alphabeta T cell receptor expression.
abstract: OBJECTIVE
  To characterise periorbital immune cells (stages, kinetics) in active and inactive thyroid associated ophthalmopathy (A-TAO; I-TAO).
  
  
  METHODS
  In orbital tissue cryosections of patients with A-TAO (n = 15), I-TAO (n = 11), and healthy controls (n = 14), adipose and fibrovascular areas were evaluated for MHC II(+) cells, CD45(+) total leukocytes, myeloid cells (CD33(+) monocytes; CD14(+) macrophages; mature RFD7(+) macrophages; RFD1(+) dendritic cells (DCs)), and lymphoid cells (CD4(+) T cells; alphabeta and gammadelta T cells; CD20(+) B cells). Results are expressed as medians and 5% confidence intervals.
  
  
  RESULTS
  In fibrovascular septae, a surge of CD33(+) immigrants clearly correlating with disease activity generated significantly increased (p<0.05) percentages of CD14(+) and RFD7(+) macrophages. Intriguingly, CD4(+) cells were mostly gammadelta T cells, while alphabeta T helper cells were much less frequent. Successful treatment rendering TAO inactive apparently downregulates monocyte influx, macrophage differentiation, and T cell receptor expression. Similar trends were recorded for adipose tissue. Interestingly, RFD1(+) DCs were completely absent from all conditions examined.
  
  
  CONCLUSIONS
  A-TAO coincides with periorbital monocyte infiltration and de novo differentiation of macrophages, but not DCs. The authors discuss a novel potential role for inflammatory CD4(+) gammadelta T cells in TAO. Successful treatment apparently downregulates orbital monocyte recruitment and effects functional T cell knockout.
authors.affiliation: Department of Ophthalmology, Essen University Hospital, Essen, Germany.
authors.forename: A K
authors.initials: AK
authors.lastname: Eckstein
authors.forename: B
authors.initials: B
authors.lastname: Quadbeck
authors.forename: S
authors.initials: S
authors.lastname: Tews
authors.forename: K
authors.initials: K
authors.lastname: Mann
authors.forename: C
authors.initials: C
authors.lastname: Krüger
authors.forename: C H
authors.initials: CH
authors.lastname: Mohr
authors.forename: K-P
authors.initials: KP
authors.lastname: Steuhl
authors.forename: J
authors.initials: J
authors.lastname: Esser
authors.forename: R K
authors.initials: RK
authors.lastname: Gieseler
mesh_terms: D000208:Acute Disease; D000273:Adipose Tissue / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D002454:Cell Differentiation; D002465:Cell Movement; D003713:Dendritic Cells / Q000276:immunology*; D006111:Graves Disease / Q000276:immunology* / Q000601:surgery; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008264:Macrophages / Q000276:immunology*; D009915:Orbit / Q000276:immunology* / Q000601:surgery; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis; D018709:Statistics, Nonparametric
chemical_list: D018950:Lipopolysaccharide Receptors; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta