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Impressum
Periocular adipose tissue in active thyroid associated ophthalmopathy (TAO) is invaded by activated inflammatory macrophages (Mo) and elevated numbers of yS-T cells
1Eckstein A., 2Quadbeck B., 3Mohr C. H., 1Steuhl K. P., 1Esser J., 2Gieseler R.
1Department of Ophthalmology, 2Department of Medicine, Division of Endocrinology; 3Department of Oral and Maxillofacial Surgery, Essen University Clinics, D-45122 Essen, Germany
Introducton: A better understanding of processes involved in the
development (TAO) require to characterize time-dependent immunologic alterations
within the different portions of orbital tissue.We here characterized
earlier identified populations of Mo and CD4+ T cells in orbital
tissues in TAO which may stimulate the increased activity of intraorbital
fibroblasts.
Methods: Surgical snap frozen orbital tissue specimens from patients
with active (n=15, A-TAO) and inactive (n=11, I-TAO) and control persons
(n=14; ptosis surgery or blepharoplasty) were stained immunohistochemically
with: CD33 (recently infiltrated monocytes), MHC II (Antigen-presenting
cells), RFD7Ag (Mature Mo) CD14 (activated tissue Mo), CD45 (all leukocytes),
CD4 (mainly T-helper cells), aß-TCR (aß-T cells),
yS-TCR (yS-T cells). Areas of AT (adipocytes only) and CT
(connective tissue strands) were evaluated separately. Medians and 5%
confidence intervals were calculated from arithmetic means of three independant
counts per section.
Results: The amount of mature (RFD7+) and inflammatory
activated (CD14+) Mo increased significantly (p<0.05) with
the diasease activity. Cell counts of the connective tissue strands: RFD7+:
A-TAO: 12.3% (0-29), I-TAO: 8.7% (0-23.5) and control: 0% (0-10.5), CD14+:
A-TAO: 14.3% (2.2-37.9), I-TAO: 1.5% (0-25.6) and control: 2.3% (0-18.7).
Most of the Mo could be proved as recent CD33+ emigrants: A-TAO:
9.3% (0-29.3), I-TAO 0.7% (0-28.1) and control: 0% (0-4.3). Interestingly,
infiltration of the CT in patients with A-TAO with yS -T cells
was more pronounced than with aß -TCR+ cells. These yS
-T cells were, again, lost to a great extent in inactive TAO (A-TAO: 7.3%
(0-39.5), I-TAO 0% (0-40), control: 0% (0-7)) The adipose tissue was less
infiltrated but revealed an equall distribution of the different cell
types.
Conclusions: Our results suggest that the therapeutic measures
taken in TAO patients may diminish factors such as facilitated adhesion
or chemotaxis which promote an influx of monocytes into orbital CT and
AT in active TAO. The Mo might be activated through the increased number
of yS -T cells. Pathologically, CD4+ yS -T cells have been
shown to be involved in autoimmune disease and can present lipid antigens,
which might apparantly play a prominent role in ocular adipose tissue.