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Comprehensive mass cytometry analysis of cell cycle, activation and coinhibitory receptors expression in CD4 T cells from healthy and HIV-infected individuals

Corneau, A., Cosma, A., Even, S. et al.

RATIONALE 
Mass cytometry allows large multiplex analysis of cell cycle stages together with differentiation, activation and exhaustion markers, allowing further assessment of the quiescence status of resting CD4 T cells.

METHODS 
Peripheral blood CD4 T lymphocytes from 8 individuals, 4 healthy donors (HD) and 4 HIV-infected on anti-retroviral treatment (T) were stained with the same 26 monoclonal antibodies and dyes targeting surface and intra-cellular markers of differentiation, activation, exhaustion and cell cycle stages. Samples were run on a CYTOF® 2.

RESULTS 
Patterns of naïve [TN] CD4 T cells strongly differed from all other memory subsets (central-memory [CM], transitional-memory [TM], effector-memory [EM] and terminally-differentiated RA-expressing [TEMRA] subsets), while stem-cell memory [SCM] and T follicular-helper cells [TfH] were close to CM and TM cells with the highest percentages in cell cycle. EM and TEMRA were the most altered by HIV infection, with an increased frequency of activated and cycling cells. Activation markers and co-inhibitory receptor expression differed among cell cycle stages, with HLA-DR fitting better than CD25 or CD38 with cycle, and opposite PD-1 gradients along differentiation and cell cycle. "Resting" DR-CD25- CD4+ T cells contained similar amounts of cells in G1 than the activated DR±CD25± ones but 3 fold lower cells in S-G2-M.

CONCLUSION 
This broad multiplex mass cytometry analysis demonstrates some subsets of the so-called "resting" CD25-DR- CD4+ T cells contain noticeable amounts of cells into cycle or expressing co-inhibitory receptors, opening new avenues for a re-definition of resting peripheral blood CD4 T cells harboring the HIV reservoirs.

Citation

Corneau, A., Cosma, A., Even, S. et al. "Comprehensive mass cytometry analysis of cell cycle, activation and coinhibitory receptors expression in CD4 T cells from healthy and HIV-infected individuals" Cytometry Part B Clinical Cytometry (2016): 21–32