Adoptive Treg Cell Therapy in a Patient With Systemic Lupus Erythematosus

被引：125

作者：

Dall'Era, Maria ^{[1
]}

Pauli, Mariela L. ^{[1
]}

Remedios, Kelly ^{[1
]}

Taravati, Keyon ^{[1
]}

Sandova, Priscila M. ^{[1
]}

Putnam, Amy L. ^{[1
]}

Lares, Angela ^{[1
]}

Haemel, Anna ^{[1
]}

Tang, Qizhi ^{[1
]}

Hellerstein, Marc ^{[2
]}

Fitch, Marc ^{[2
]}

McNamara, James ^{[3
]}

Welch, Beverly ^{[3
]}

Bluestone, Jeffrey A. ^{[1
]}

Wofsy, David ^{[1
]}

Rosenblum, Michael D. ^{[1
]}

机构：

[1] Univ Calif San Francisco, San Francisco, CA 94143 USA

[2] Univ Calif Berkeley, Berkeley, CA 94720 USA

[3] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA

来源：

ARTHRITIS & RHEUMATOLOGY | 2019年 / 71卷 / 03期

关键词：

REGULATORY T-CELLS; SUBSETS; AUTOIMMUNE;

D O I：

10.1002/art.40737

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Objective Adoptive Treg cell therapy has great potential to treat autoimmune disease. Currently, very little is known about how these cells impact inflamed tissues. This study was undertaken to elucidate how autologous Treg cell therapy influences tissue inflammation in human autoimmune disease. Methods We describe a systemic lupus erythematosus (SLE) patient with active skin disease who received adoptive Treg therapy. We comprehensively quantified Treg cells and immune activation in peripheral blood and skin, with data obtained at multiple time points posttreatment. Results Deuterium tracking of infused Treg cells revealed the transient presence of cells in peripheral blood, accompanied by increased percentages of highly activated Treg cells in diseased skin. Flow cytometric analysis and whole transcriptome RNA sequencing revealed that Treg cell accumulation in skin was associated with a marked attenuation of the interferon-gamma pathway and a reciprocal augmentation of the interleukin-17 (IL-17) pathway. This phenomenon was more pronounced in skin relative to peripheral blood. To validate these findings, we investigated Treg cell adoptive transfer of skin inflammation in a murine model and found that it also resulted in a pronounced skewing away from Th1 immunity and toward IL-17 production. Conclusion We report the first case of a patient with SLE treated with autologous adoptive Treg cell therapy. Taken together, our results suggest that this treatment leads to increased activated Treg cells in inflamed skin, with a dynamic shift from Th1 to Th17 responses.

引用

页码：431 / 440

页数：10

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