AIMS: Mucosal Associated Invariant T (MAIT) cells are unconventional T cells with anti-infective potential. MAIT cells detect and fight against microbes on mucosal surfaces and in peripheral tissues. Previous works suggested that MAIT cells survive exposure to cytotoxic drugs in these locations. We sought to determine if they maintain their anti-infective functions after myeloablative chemotherapy. METHODS: We correlated the amount of MAIT cells (measured by flow cytometry) in the peripheral blood of 100 adult patients before the start of myeloablative conditioning plus autologous stem cell transplantation with the clinical and laboratory outcomes of aplasia. RESULTS: The amount of MAIT cells negatively correlated with peak C-reactive protein level and the amount of red blood cell transfusion units resulting in earlier discharge of patients with the highest amount of MAIT cells. CONCLUSION: This work suggests the anti-infectious potential of MAIT cells is maintained during myeloid aplasia.

• Keywords
• ASCT, MAIT cells, complications, infection,
• MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Mucosal-Associated Invariant T Cells * immunology   MeSH
• Young Adult MeSH
• Lymphocyte Count MeSH
• Transplantation Conditioning methods   MeSH
• Flow Cytometry MeSH
• Aged MeSH
• Hematopoietic Stem Cell Transplantation MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Psoriasis vulgaris (PV) is a chronic, recurrent inflammatory dermatosis mediated by aberrantly activated immune cells. The role of the innate-like T cells, particularly gammadelta T (γδT) cells and MR1-restricted T lymphocytes, is incompletely explored, mainly through animal models, or by use of surrogate lineage markers, respectively. Here, we used case-control settings, multiparameter flow cytometry, 5-OP-RU-loaded MR1-tetramers, Luminex technology and targeted qRT-PCR to dissect the cellular and transcriptional landscape of γδ and MR1-restricted blood T cells in untreated PV cases (n=21, 22 matched controls). High interpersonal differences in cell composition were observed, fueling transcriptional variability at healthy baseline. A minor subset of canonical CD4+CD8+MR1-tet+TCRVα7.2+ and CD4+CD8-MR1-tet+TCRVα7.2+ T cells was the most significantly underrepresented community in male PV individuals, whereas Vδ2+ γδ T cells expressing high levels of TCR and Vδ1-δ2- γδ T cells expressing intermediate levels of TCR were selectively enriched in affected males, partly reflecting disease severity. Our findings highlight a formerly unappreciated skewing of human circulating MAIT and γδ cytomes during PV, and reveal their compositional changes in relation to sex, CMV exposure, serum cytokine content, BMI, and inflammatory burden. Complementing numerical alterations, we finally show that flow-sorted, MAIT and γδ populations exhibit divergent transcriptional changes in mild type I psoriasis, consisting of differential bulk expression for signatures of cytotoxicity/type-1 immunity (EOMES, RUNX3, IL18R), type-3 immunity (RORC, CCR6), and T cell innateness (ZBTB16).

• Keywords
• MR1, cytokines, gammadelta T lymphocytes, mucosal associated invariant T cells, psoriasis,
• MeSH
• Cell Differentiation MeSH
• Cytotoxicity, Immunologic MeSH
• Adult MeSH
• Blood Circulation MeSH
• Middle Aged MeSH
• Humans MeSH
• Mucosal-Associated Invariant T Cells immunology   MeSH
• Histocompatibility Antigens Class I metabolism   MeSH
• Young Adult MeSH
• Immunity, Innate MeSH
• Promyelocytic Leukemia Zinc Finger Protein genetics   metabolism   MeSH
• Psoriasis immunology   MeSH
• Receptors, Antigen, T-Cell, gamma-delta metabolism   MeSH
• T-Lymphocytes immunology   MeSH
• Th1 Cells immunology   MeSH
• Minor Histocompatibility Antigens metabolism   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Histocompatibility Antigens Class I MeSH
• MR1 protein, human MeSH Browser
• Promyelocytic Leukemia Zinc Finger Protein MeSH
• Receptors, Antigen, T-Cell, gamma-delta MeSH
• Minor Histocompatibility Antigens MeSH

Immune reconstitution after high-dose chemotherapy and stem cell transplantation plays a key role in restoring immunocompetence including defense against infection, immune regulation, and onco-immune surveillance. In this work, we examined the recovery of mucosal-associated invariant T (MAIT) cells, recently discovered innate-like T cells, after various types of myeloablative chemotherapy and autologous peripheral blood stem cell transplantation in 29 patients. We show that MAIT cells are relatively resistant to myeloablative conditioning. The median amount of MAIT cells rises to 43 % around day +30 and is sustained through further measurements on days +60 and +100. Moreover, MAIT cell recovery reaches 100 % of pre-treatment values in 33 % of patients already by day +60. The only factor affecting recovery of MAIT cells is age, younger age being associated with earlier MAIT cell recovery. The pre-treatment quantity of MAIT cells carries a prognostic impact on the early post-transplantation course. Patients with high levels of MAIT cells pre-treatment have significantly lower peak CRP levels (79.45 vs. 150 mg/L) post-treatment, reflecting a clinical trend of less severe infectious complications (less febrile days and less days on intravenous antibiotics). Altogether these data suggest that a high proportion of MAIT cells survive myeloablative chemotherapy and maintain their capacity to fight against infections probably on mucosal surfaces.

• Keywords
• Autologous peripheral blood stem cell transplantation, Complications, MAIT cells, Myeloablative chemotherapy, Recovery,
• MeSH
• Transplantation, Autologous methods   MeSH
• C-Reactive Protein metabolism   MeSH
• Cytarabine administration & dosage   pharmacology   MeSH
• Hematologic Neoplasms blood   immunology   therapy   MeSH
• Carmustine administration & dosage   pharmacology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Mucosal-Associated Invariant T Cells drug effects   metabolism   MeSH
• Melphalan administration & dosage   pharmacology   MeSH
• Myeloablative Agonists administration & dosage   pharmacology   MeSH
• Podophyllotoxin administration & dosage   pharmacology   MeSH
• Transplantation Conditioning methods   MeSH
• Antineoplastic Combined Chemotherapy Protocols administration & dosage   pharmacology   MeSH
• Peripheral Blood Stem Cell Transplantation methods   MeSH
• Age Factors MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• C-Reactive Protein MeSH
• Cytarabine MeSH
• Carmustine MeSH
• Melphalan MeSH
• Myeloablative Agonists MeSH
• Podophyllotoxin MeSH