Short communicationCharacterization of natural killer cells in paired CSF and blood samples during neuroinflammation
Introduction
Over the past decade, the importance of natural killer (NK) cells in regulating immunological processes has been acknowledged. Human NK cells are classically categorized into two major subsets based on the expression of different levels of CD56. While the majority of the circulating NK cells are highly cytotoxic CD56dim cells, about 10% are immature bright CD56 expressers (CD56bright) that display imunomodulatory functions and have been implicated in the beneficial effects of novel MS treatments such as daclizumab (Bielekova et al., 2006). In this line, we previously reported an elevated frequency of circulating CX3CR1-NK cells in stable but not in active MS patients (Infante-Duarte et al., 2005). Soon after, we showed that CX3CR1‐NK cells were indeed immature NK cells and that the chemokine receptor CX3CR1 may serve in combination with CD56, CD57, CD62L, and CD27 to define different steps of NK cell maturation (Hamann et al., 2011).
Despite numerous recent studies on the implications of NK cells in chronic and autoimmune diseases, the magnitude of the influence of NK cells in inflammatory CNS disorders so far remains elusive, partly due to the lack of compelling studies on NK cell trafficking into the CNS.
Therefore, to characterize NK cell trafficking into the CSF, we determined the frequencies and phenotype of NK cells in CSF from patients with MS, other inflammatory neurological diseases (IND) and non-inflammatory neurological diseases (NIND), and related the analyses to the data obtained from the corresponding paired peripheral blood samples.
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Study population
We analyzed a total of 62 paired CSF and blood samples obtained at the Cleveland Clinic, Cleveland, Ohio, USA and at the Charité — Universitätsmedizin Berlin, Germany. Patient groups showed comparable age and female:male ratios and included in total 22 patients with definite multiple sclerosis (MS) according to the 2005 McDonald criteria (Polman et al., 2005), 11 with other inflammatory neurological diseases (IND) and 29 patients with non-inflammatory neurological diseases (NIND). Demographics
Decreased NK cell frequency in the CSF of MS patients
CSF and blood samples from patients (comparable age and female:male ratios) with definite MS (n = 16), IND (n = 8) and NIND (n = 29) were stained with antibodies against CD3, CD16 and CD56 (Fig. 1A). Frequencies of CSF NK cells (CD16+CD56+CD3-lymphocytes) as well as CD56+CD16+CD3+ NKT cells and CD3+ T cells were compared to their counterparts in the blood. We found a decreased frequency of NK cells in the CSF of patients with MS compared to NIND patients (MS: 2.7 ± 2.1%; IND: 3.2 2.1%; NIND: 4.5 ± 2.7%) (
Discussion
Confirming our previous data (Infante-Duarte et al., 2005), similar percentages of blood NK cells were detected in MS and IND or NIND patients. However, we found a decreased frequency of CSF NK cells in MS patients compared to the other investigated pathologies, which is in agreement with the reported decreased NK cell activities in MS CSF compared to other conditions (Salmaggi et al., 1989). Since in MS patients the frequencies of T lymphocytes in CSF remained comparable to those observed
Acknowledgments
This work was supported by the Deutsche Forschungsgemeinschaft (SFB 650 and Exc. 257), by a grant to C.ID. from the European Community's Seventh Framework Programme (UEPHA*MS, Grant agreement # 212877) and by a grant from the Charité (Rahel-Hirsch stipend) to C.ID. We thank Dr. Javier Provencio for providing patient material. Barbara Tuckey, Anna Rietsch and Thordis Hohnstein for excellent technical assistance.
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