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Published on: February 5, 2015
Specific alterations in NKG2D+ T lymphocytes in relapsing-remitting and progressive multiple sclerosis patients
Ana Carmena Moratalla1, Yves Carpentier Solorio1, Florent Lemaître1
1Department of Neurosciences, Université de Montréal and Centre de Recherche du CHUM (CRCHUM) 900 St-Denis Street Montreal, QC, Canada, H2X0A9.
Background:
T lymphocytes exhibit numerous alterations in relapsing-remitting (RRMS), secondary progressive (SPMS), and primary progressive multiple sclerosis (PPMS). The NKG2D pathway has been involved in MS pathology. NKG2D is a co-activating receptor on subsets of CD4+ and most CD8+ T lymphocytes. The ligands of NKG2D are expressed at low levels in normal tissues but are elevated in MS postmortem brain tissues compared with controls. Whether the NKG2D pathway shows specific changes in different forms of MS remains unclear.
Methods:
We performed unsupervised and supervised flow cytometry analysis to characterize peripheral blood T lymphocytes from RRMS, SPMS, and PPMS patients and healthy controls (HC). We used an in vitro microscopy approach to assess the role of NKG2D in the interactions between human CD8+T lymphocytes and human astrocytes.
Results:
Specific CD8+, CD4+, and CD4-CD8- T cell populations exhibited altered frequency in MS patients' subgroups. The proportion of NKG2D+ T lymphocytes declined with age in PPMS patients but not in RRMS and HC. This reduced percentage of NKG2D+ cells was due to lower abundance of γδ and αβ CD4-CD8- T lymphocytes in PPMS patients. NKG2D+ T lymphocytes were significantly less abundant in RRMS than in HC; this was caused by a decreased frequency of CD4-CD8- and CD8+ T lymphocytes and was not linked to age. Blocking NKG2D increased the motility of CD8+ T lymphocytes co-cultured with astrocytes expressing NKG2D ligand. Moreover, preventing NKG2D from interacting with its ligands increased the proportion of CD8+ T lymphocytes exhibiting a kinapse-like behavior characterized by short-term interaction while reducing those displaying a long-lasting synapse-like behavior. These results support that NKG2D participates in the establishment of long-term interactions between activated CD8+ T lymphocytes and astrocytes.
Conclusion:
Our data demonstrate specific alterations in NKG2D+ T lymphocytes in MS patients' subgroups and suggest that NKG2D contributes to the interactions between human CD8+ T lymphocytes and human astrocytes.
Insights
NKG2D+ T lymphocytes show distinct changes in different multiple sclerosis (MS) forms. This pathway influences interactions between CD8+ T cells and astrocytes, impacting MS pathology.
Area of Science:
- Immunology
- Neuroscience
- Cell Biology
Background:
- T lymphocytes are altered in relapsing-remitting (RRMS), secondary progressive (SPMS), and primary progressive multiple sclerosis (PPMS).
- The NKG2D pathway, involving T lymphocytes, is implicated in MS pathology, with elevated NKG2D ligands in MS brain tissue.
- Specific changes in the NKG2D pathway across different MS forms remain unclear.
Purpose of the Study:
- To investigate alterations in NKG2D+ T lymphocytes in various forms of multiple sclerosis (MS).
- To explore the role of the NKG2D pathway in CD8+ T lymphocyte interactions with astrocytes in MS.
Main Methods:
- Flow cytometry was used to analyze peripheral blood T lymphocytes from RRMS, SPMS, PPMS patients, and healthy controls (HC).
- In vitro microscopy assessed the role of NKG2D in CD8+ T lymphocyte and astrocyte interactions.
Main Results:
- Altered frequencies of specific T cell populations (CD8+, CD4+, CD4-CD8-) were observed in MS subgroups.
- NKG2D+ T lymphocyte proportion declined with age in PPMS and was reduced in RRMS compared to HC, linked to specific T cell subset changes.
- Blocking NKG2D affected CD8+ T lymphocyte motility and synapse formation with astrocytes, indicating NKG2D's role in T cell-astrocyte interactions.
Conclusions:
- Specific alterations in NKG2D+ T lymphocytes are present in distinct MS patient subgroups.
- The NKG2D pathway plays a role in mediating interactions between human CD8+ T lymphocytes and astrocytes in the context of MS.
