Differential Expression of CD11c by Peripheral Blood NK Cells Reflects Temporal Activity of Multiple Sclerosis

Abstract

Multiple sclerosis (MS) is an autoimmune disease, showing a great degree of variance in temporal disease activity. We have recently demonstrated that peripheral blood NK cells biased for secreting IL-5 (NK2 bias) are associated with the remission state of MS. In this study, we report that MS patients in remission differentially express CD11c on NK cell surface (operationally defined as CD11chigh or CD11clow). When we compared CD11chigh or CD11clow patients, the expression of IL-5 and GATA-3 in NK cells supposed to endow a disease-protective NK2 phenotype was observed in CD11clow but not in CD11chigh patients. In contrast, the CD11chigh group showed a higher expression of HLA-DR on NK cells. In vitro studies demonstrated that NK cell stimulatory cytokines such as IL-15 would up-regulate CD11c expression on NK cells. Given previous evidence showing an association between an increased level of proinflammatory cytokines and temporal disease activity in MS, we postulate that inflammatory signals may play a role in inducing the CD11chigh NK cell phenotype. Follow-up of a new cohort of patients showed that 6 of 10 CD11chigh MS patients developed a clinical relapse within 120 days after evaluation, whereas only 2 of 13 CD11clow developed exacerbated disease (p = 0.003). As such, a higher expression of CD11c on NK cells may reflect the temporal activity of MS as well as a loss of regulatory NK2 phenotype, which may allow us to use it as a potential biomarker to monitor the immunological status of MS patients.

Loss of Cytotoxicity and Gain of Cytokine Production in Murine Tumor-Activated NK Cells

“…Although both CD56 br ight and CD11c dim human NK cells have been correlated with multiple sclerosis activity [17], [18], [35], differences in the CD11c expression have not been reported for human NK cell subsets. Analyzing PBMCs from normal donors we observed that CD3 − /CD56 dim NK cells contained a sub-population that expressed high amounts of CD11c (Fig.…”

Regulatory Functions of Natural Killer Cells in Multiple Sclerosis

“…Among these patients, a further division of NK2 cells as CD11c-high (not producing IL-5) and CD11c-low (producing IL-5) subsets identified CD11c-high patients at risk of relapse (49), suggesting that CD11c + NK cells are pro-inflammatory. In another study, a subpopulation of NK cells characterized by low expression of CD8, a phenotype associated with CD56 bright NK cells, was observed to be reduced in untreated patients with relapsing-remitting MS (50).…”

Dynamic change in natural killer cell type in the human ocular mucosa in situ as means of immune evasion by adenovirus infection

“…[18][19][20][21] HLA-DR is suitable for this purpose as it is expressed stably for a long duration on activated lymphocytes. 18,21 We found that NKG2A À CD56 dim conjunctiva NK cells were the only activated NK subset, and HLA-DR was not upregulated in the CD56 bright NK cells and NKG2A þ CD56 dim NK cells (Figure 3f,g). CD38 expression was similar to that of HLA-DR where higher expression levels were observed on CD56 dim NK cells and CD56 dim NKG2A À NK cells as compared with CD56 bright and CD56 dim NKG2A þ NK cells respectively (Figure 3h, top panel).…”