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

We sought to determine whether the predominant orbital T helper (T_H) 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_H1-type clones were predominant in cultures from patients with recent onset (<2 yr) Graves' hyperthyroidism (n = 44; T_H1/T_H0/T_H2 = 57/29/14%) or GO (n = 53 clones; T_H1/T_H0/T_H2 = 47/30/23%). In contrast, T_H2-type clones predominated in cultures from patients with more remote onset (>2 yr) hyperthyroidism (n = 13; T_H1/T_H0/T_H2 = 0/31/69%;P < 0.005) or GO (n = 4; T_H1/T_H0/T_H2 = 0/25/75%; P = 0.05). In addition, we established T cell clones from 1 T_H1-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_H2-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_H1-type) immune reactions may predominate in the orbit in early GO, whereas humoral immunity (T_H2-type) might play the greater role in later stages of the disease.