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Regulatory T cells (red), shown in a sarcoidosis granuloma, inhibit T cell proliferation, but not their cytokine production.

Sarcoidosis is a mysterious, long-recognized disease characterized by the formation of tuberculosis-like granulomas in the lungs. The mystery of sarcoidosis stems from both its unknown etiology and its paradoxical effects on the immune system. The disease has been attributed to a hyperactivation of CD4⁺ T helper type 1 cells that infiltrate the lungs but, in patients with sarcoidosis, these very cells fail to proliferate in response to recall antigens.

On page 359, Miyara and colleagues suggest that half-cocked regulatory T (T reg) cells that inhibit proliferation by T cells but not their cytokine production might be to blame for this immune contradiction.

T reg cells normally help suppress chronic inflammation by inhibiting both effector T cell proliferation and cytokine production. Miyara et al. now show that although T reg cell numbers are elevated in both the blood and the lungs of patients with sarcoidosis, these cells were unable to curb the CD4⁺ T cell production of TNF and interferon (IFN)-—inflammatory cytokines that drive the formation and maintenance of granulomas. However, the patients' T reg cells could still shut down effector T cell proliferation, possibly explaining the inability of T cells to respond to recall antigens.

The mechanism behind the T reg cell defect in patients with sarcoidosis remains to be defined, but might be a byproduct of chronic inflammation, as half-active T reg cells have also been found in autoimmune inflammatory diseases such as rheumatoid arthritis and multiple sclerosis.

hvanepps{at}rockefeller.edu

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Related Article

The immune paradox of sarcoidosis and regulatory T cells

Makoto Miyara, Zahir Amoura, Christophe Parizot, Cécile Badoual, Karim Dorgham, Salim Trad, Marianne Kambouchner, Dominique Valeyre, Catherine Chapelon-Abric, Patrice Debré, Jean-Charles Piette, and Guy Gorochov
J. Exp. Med. 2006 203: 359-370. [Abstract] [Full Text] [PDF]

This Article PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Van Epps, H. L. Search for Related Content PubMed Articles by Van Epps, H. L. Related Collections Related Article Social Bookmarking                            What's this?