Relationship between disease duration and predominant orbital T cell subset in Graves' ophthalmopathy

We sought to determine whether the predominant orbital T helper (T,) cell subset in orbital T cell clones established from patients with Graves' ophthalmopathy (GO) might be related to disease duration. A total of 117 clones were established from orbital adipose/connective tissues of 6 GO patients, and cytokine production was measured in 57 CD3(+)CD4(+) clones. T(H)1-type clones were predominant in cultures from patients with recent onset (<2 yr) Graves' hyperthyroidism(n = 44; T(H)1/T(H)0/T(H)2 = 57/29/14%) or GO (n = 53 clones; T(H)1/T(H)0/T(H)2 = 47/30/23%). In contrast, T(H)2-type clones predominated in cultures from patients with more remote onset (>2 yr) hyperthyroidism (n = 13; T(H)1/T(H)0/T(H)2 = 0/31/69%; P < 0.005) or GO (n = 4; T(H)1/T(H)0/T(H)2 = 0/25/75%; P = 0.05). In addition, we established T cell clones from 1 T(H)1-dominant patient with recent-onset thyroid and eye disease using either IL-2 (12.5 ng/mL) alone or IL-2 plus IL-4 (5 ng/mL) and found no shift toward recovery of T(H)2-type clones in the latter. In conclusion, although the CD3(+)CD4(+) clones characterized were not necessarily tissue antigen specific, our findings suggest that cell-mediated (T(H)1-type) immune reactions may predominate in the orbit in early GO, whereas humoral immunity (T(H)2-type) might play the greater role in later stages of the disease.