Project 451691

In lupus, antibodies are mistakenly produced against molecules that are part of the body, such as DNA and other proteins found in the nuclei of cells (ANAs), which then deposit in the organs causing inflammation and damage. Lupus follows an unpredictable course, with periods of remission and exacerbation (flares). Currently, the immune mechanisms that produce flares are unknown. We and others have shown that production of ANAs requires the cooperation of two different types of immune cells, B cells and T cells. While it is the B cells that ultimately become the ANA-secreting cells, they require help from T cells to acquire this ability. There are a number of different types of T cells and currently the properties of the T cells that cause flares are not known. To study this question we examined the T cells in the blood of SLE patients who had a recent flare and those who had not flared for at least 2 years. We also examined how the T cells in the blood changed over time following treatment. We found that based upon the types of T cells that were in the blood at or following flares, patients could be categorized into two groups. In this study, we seek to further characterize the functional characteristics of T cells in these two groups and to investigate whether they differ in the mechanisms by which they promote tissue inflammation in flares. Our experiments may pave the way to new therapies for treatment of lupus.