This study aimed to characterize the expression patterns of CD158 subsets (A, B, B2, H, and I) in NK and NKT cells across various neuroinflammatory conditions, including myelin oligodendrocyte glycoprotein antibody disease (MOGAD), neuromyelitis optica spectrum disorders (NMOSD), and multiple sclerosis (MS).

Killer cell Immunoglobulin-like Receptors (KIRs or CD158 molecules) are expressed on Natural Killer (NK) and Natural Killer T (NKT) cells, interacting with MHC class I molecules on target cells to mediate self-recognition and tolerance. We explored the expression patterns of KIRs on NK/NKT cells in neuroinflammatory diseases.

A total of 35 peripheral blood mononuclear cell samples from patients with NMOSD, MS, MOGAD, and healthy controls were analyzed using flow cytometry. The expression of KIR molecules on NK and NKT cells was assessed using markers for CD158 subsets (inhibitory KIRs: CD158A, B, and B2; activating KIR: CD158H and I), along with CD16, CD57, and CD88.

NK and NKT cells exhibited distinct KIR expression patterns. NK cells, particularly CD57⁺ NK cells, showed higher expression of inhibitory KIRs (CD158A, B, and B2), while NKT cells predominantly expressed CD158I. KIR expression levels on NK and NKT cells did not significantly differ among disease groups. Analysis of CD158-positive subsets revealed broad CD16 expression in NK cells expressing any studied KIRs, whereas in NKT cells, CD16 expression was observed in CD158H-positive cells. High CD88 expression in CD158H⁺ NK and NKT cells was observed particularly in MOGAD and NMOSD groups.

The distinct expression patterns of KIRs on NK and NKT cells and their co-expression with CD16 and CD57 suggest specialized roles for these activating or inhibitory receptors in immune regulation. Further research is needed to elucidate the specific functions of each KIR molecule and the interplay between KIRs and their ligands in the context of neuroinflammation.