Richard Burt, MD, Northwestern University School of Medicine

"Unusual Regulatory T Cells in Patients with Severe Lupus Following HSCT"

2009 Adult Stem Cell Grant Award

These grant awards are made possible through support by the Cooper Family Foundation

Researchers at Northwestern University have found that regulatory T cells (Treg) return in patients with refractory lupus after stem cell transplantation, and both CD4+CD25HighFoxP3+, and an unusual CD8+FoxP3+ Treg subsets are increased. Observations in mouse models of SLE suggest that induced CD8+ Treg cells are important in controlling lupus. Researchers aim to characterize the CD8 Treg subset of post-transplant lupus patients with regards to their unique surface markers, cytokine/chemokine profile, and mechanism of action. Clinical correlations based on gender and disease activity will be done. Molecular requirements for both nuclear autoantigen-specific and non-specific suppressive function of the Treg will be determined. Significance to gaps in knowledge relevant to lupus. The mechanisms of long-term remission of lupus after stem cell transplantation are unknown. Our hypothesis is that the therapy generates a newly differentiated population of Treg cells, which repairs the Treg deficiency in lupus. Defects in Treg cells are beginning to be described in lupus patients. Most of those studies deal with phenotyping and enumerating the CD4+CD25High Treg subset by surface markers. Functional studies, especially autoantigen-specific suppression have not been done. Moreover, very little is known about unusual CD8+ Treg cells in humans and how they could control lupus autoimmunity, although animal models indicate their importance. Investigators will evaluate the quality and quantity of Treg cells before and after HSCT and compare their recovery to gender and clinical disease status. Therefore, this proposal will address new issues critical for immunoregulation of lupus autoimmunity and therapy.