From cancerous and non-cancerous patients, we derived stable clones of CD4 1 Treg, defined as clones that expressed high CD25 at rest, were anergic in vitro, and suppressed the proliferation of co-cultured CD4 1 cells. A conserved region of FOXP3 intron 1 was demethylated in all Treg clones, whereas it was methylated in non-regulatory Th and CTL clones. In our panel of human clones, this stable epigenetic mark correlated better with suppressive activity than did FOXP3 mRNA or protein expression. We used expression microarrays to compare Treg and Th clones after activation, which is required for suppressive function. The transcriptional profile that is specific of activated Treg clones includes a TGF-b signature. Both activated Treg and Th clones produced the latent form of TGF-b. However, SMAD2 phosphorylation was observed after activation in the Treg but not in the Th clones, indicating that only activated Treg clones produced the bioactive form of TGF-b. A TGF-b signature was also displayed by a Th clone ''suppressed'' by a Treg clone. In conclusion, the hallmark of our panel of activated human Treg clones is to produce bioactive TGF-b which has autocrine actions on Tregs and can have paracrine actions on other T cells.

The presence of the CCR5Delta32 polymorphism in patients with stage IV melanoma results in a decreased survival following immunotherapy and may help to select patients less likely to benefit from this type of treatment.

The authors report on the case of a 37-year-old woman in whom a primary sellar malignant melanoma mimicking a hemorrhagic pituitary macroadenoma was treated. This entity is exceedingly rare; only five cases are described in the literature. The patient presented with rapid deterioration of vision within a 2-week period. After an ophthalmological diagnosis of chiasmal syndrome was made, magnetic resonance (MR) imaging of the head revealed an intra- and suprasellar mass that was elevating and compressing the optic chiasm. Because of the signal heterogeneity of the lesion a hemorrhagic pituitary macroadenoma was assumed; the lesion was transsphenoidally resected. Histological examination of the specimen showed a malignant melanocytic tumor with immunopositivity for S100 protein and HMB-45. Despite extensive staging no other primary melanotic tumor was found. Thus, a primary sellar melanoma was diagnosed. Postoperative MR images demonstrated no residual tumor. For adjuvant therapy the region around the sella turcica received 40.4 Gy stereotactically guided radiation. A 24-month follow-up examination revealed no tumor recurrence. This represents the sixth case of such a lesion reported in the literature, the third case evaluated using MR imaging, and the first case with a progression-free survival of 24 months. Thus, the authors advocate that management of primary sellar melanoma should include gross-total removal and postoperative stereotactic radiotherapy.