MAIT Cell Frequency Research Articles

O034 : Frequency and function of anti-bacterial mait cells are significantly impaired in advanced alcoholic liver disease

O034 : Frequency and function of anti-bacterial mait cells are significantly impaired in advanced alcoholic liver disease

Mucosal-associated invariant T cell deficiency in systemic lupus erythematosus.

Mucosal-associated invariant T (MAIT) cells contribute to protection against certain microorganism infections and play an important role in mucosal immunity. However, the role of MAIT cells remains enigmatic in autoimmune diseases. In this study, we examined the level and function of MAIT cells in patients with rheumatic diseases. MAIT cell, cytokine, and programmed death-1 (PD-1) levels were measured by flow cytometry. Circulating MAIT cell levels were significantly reduced in systemic lupus erythematosus (SLE) and rheumatoid arthritis patients. In particular, this MAIT cell deficiency was more prominent in CD8(+) and double-negative T cell subsets, and significantly correlated with disease activity, such as SLE disease activity index and 28-joint disease activity score. Interestingly, MAIT cell frequency was significantly correlated with NKT cell frequency in SLE patients. IFN-γ production in MAIT cells was impaired in SLE patients, which was due to an intrinsic defect in the Ca(2+)/calcineurin/NFAT1 signaling pathway. In SLE patients, MAIT cells were poorly activated by α-galactosylceramide-stimulated NKT cells, thereby showing the dysfunction between MAIT cells and NKT cells. Notably, an elevated expression of PD-1 in MAIT cells and NKT cells was associated with SLE. In rheumatoid arthritis patients, MAIT cell levels were significantly higher in synovial fluid than in peripheral blood. Our study primarily demonstrates that MAIT cells are numerically and functionally deficient in SLE. In addition, we report a novel finding that this MAIT cell deficiency is associated with NKT cell deficiency and elevated PD-1 expression. These abnormalities possibly contribute to dysregulated mucosal immunity in SLE.

O-064 Development And Maturation Of Mait Cells In Human Neonates: Relations With Gestational Age And Microbial Infection

Newborns , in particular preterm neonates, suffer a high frequency of microbial infections. MAIT cells are innate-like T cells expressing a semi-invariant Vα7.2-Jα33 TCR which recognises MR1-restricted, microbial-derived riboflavin (vitamin B2) metabolites unique to bacteria and yeast. We studied 151 newborns admitted in the Neonatology Department at Robert Debre Hospital divided into four groups according to gestational age (group 1: 24–27 wks; group 2: 28–31 wks; group 3: 32–36 wks; group 4: >37 wks). The rate and kinetics of MAIT cell expansion and maturation were determined longitudinally at birth (day 0), day 3, day 30 and day 60. We performed multiparametric 10-colour flow cytometry analyses using combinations of antibodies to CD45, CD3, CD4, CD8, TCR Vα7.2, CD161, CD45RA, TCR Vα24 and TCRγδ on 100 ml residual whole blood (left over of blood count), allowing characterisation of MAIT cells in parallel with other non-conventional and conventional T cells. Our results show that the frequency of MAIT at birth is low and significantly differs according to gestational age (median at D0 group 1: 0.21%; group 2: 0.14%; group 3: 0.12%; group 4: 0.06%). Of note, this frequency remains relatively stable over the first 2 months of life. However, the phenotype of MAIT cell changes after birth with rapid maturation and increased proportion of CD8aa cells. Significant difference was observed between high preterm neonates with and without maternofetal infection. Analysis of MAIT cell frequency in 20 twin pairs showed it was very similar, suggesting that it might be controlled by a genetic and/or early environmental factor. In conclusion, the frequency of MAIT cells at birth is inversely correlated with gestational age, and is correlated with the presence of maternofetal microbial infection in preterm neonates. Whether it may reflect the presence of microbial products in amniotic liquid, and/or differences in the gut microbiota immediately after birth is under investigation.

CD8⁺ MAIT cells infiltrate into the CNS and alterations in their blood frequencies correlate with IL-18 serum levels in multiple sclerosis.

Recent findings indicate a pathogenic involvement of IL-17-producing CD8(+) Tcells in multiple sclerosis (MS). IL-17 production has been attributed to a subset of CD8(+) Tcells that belong to the mucosal-associated invariant T (MAIT) cell population. Here, we report a reduction of CD8(+) MAIT cells in the blood of MS patients compared with healthy individuals, which significantly correlated with IL-18 serum levels in MS patients. In vitro stimulation of peripheral blood mononuclear cells from healthy individuals and MS patients with IL-18 specifically activated CD8(+) MAIT cells. Moreover, IL-18 together with T-cell receptor stimulation induced, specifically on CD8(+) MAIT cells, an upregulation of the integrin very late antigen-4 that is essential for the infiltration of CD8(+) Tcells into the CNS. Notably, we were able to identify CD8(+) MAIT cells in MS brain lesions by immunohistochemistry while they were almost absent in the cerebrospinal fluid (CSF). In summary, our findings indicate that an IL-18-driven activation of CD8(+) MAIT cells contributes to their CNS infiltration in MS, in turn leading to reduced CD8(+) MAIT-cell frequencies in the blood. Therefore, CD8(+) MAIT cells seem to play a role in the innate arm of immunopathology in MS.