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.
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.
Eckstein
A K
AK
Department of Ophthalmology, Essen University Hospital, Essen, Germany.
Quadbeck
B
B
Tews
S
S
Mann
K
K
Krüger
C
C
Mohr
C H
CH
Steuhl
K-P
KP
Esser
J
J
Gieseler
R K
RK
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
D018950:Lipopolysaccharide Receptors; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta