title: High content cellular immune profiling reveals differences between rhesus monkeys and men.
abstract: A better understanding of similarities and differences in the composition of the cellular immune system in non-human primates (NHPs) compared with human subjects will improve the interpretation of preclinical studies. It will also aid in addressing the usefulness of NHPs as subjects for studying chronic diseases, vaccine development and immune reconstitution. We employed high content colour flow cytometry and analysed simultaneously the expression of CD3, CD4, CD8alpha, CD8beta, CD16/CD56, CD45RA, CCR7, CD27, CD28, CD107a and the interleukin-7 receptor alpha-chain (IL-7Ralpha) in peripheral blood mononuclear cells (PBMCs) of 27 rhesus macaques and 16 healthy human subjects. Regulatory T cells (Tregs) were identified using anti-CD3, -CD4, -CD25, -FoxP3, and -IL-7Ralpha monoclonal antibodies. Responsiveness to IL-7 was gauged in a signal transducer and activation of transcription 5 (STAT-5) phosphorylation assay. Human and NHP PBMCs showed a similar T-cell composition pattern with some remarkable differences. Similarities: human and NHP CD4(+) and CD8(+) cells showed a similar STAT-5 phosphorylation pattern in response to IL-7. Multicolour flow cytometric analysis identified a CD4(+) CD8alphaalpha(+) CD8alphabeta(+) T-cell population in NHPs as well as in human subjects that expressed the degranulation marker CD107a and may represent a unique CD4(+) T-cell subset endowed with cytotoxic capacity. Differences: we identified in PBMCs from NHPs a higher proportion (5.16% in CD3(+) T cells) of CD8alphaalpha(+) T cells when compared with human donors (1.22% in CD3(+) T cells). NHP CD8alphaalpha(+) T cells produced tumour necrosis factor-alpha / interferon-gamma (TNF-alpha/IFN-gamma) or TNF-alpha, whereas human CD8alphaalpha(+) T cells produced simultaneously TNF-alpha/IFN-gamma and IL-2. A minor percentage of human CD8(+) T cells expressed CD25(bright) and FoxP3 (0.01%). In contrast, 0.07% of NHP CD8(+) T cells exhibited the CD25(bright) FoxP3(+) phenotype. PBMCs from NHPs showed less IL-7Ralpha-positive events in all T-cell subsets including CD4(+) Tregs (median 5%) as compared with human (median 12%). The data visualize commonalities and differences in immune cell subsets in humans and NHPs, most of them in long-lived memory cells and cells with suppressive functions. This provides a matrix to assess future efforts to study diseases and vaccines in NHPs.
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Solna, Sweden..
authors.forename: Isabelle
authors.initials: I
authors.lastname: Magalhaes
authors.forename: Nalini K
authors.initials: NK
authors.lastname: Vudattu
authors.forename: Raija K
authors.initials: RK
authors.lastname: Ahmed
authors.forename: Sharon
authors.initials: S
authors.lastname: Kühlmann-Berenzon
authors.forename: Yen
authors.initials: Y
authors.lastname: Ngo
authors.forename: Donata R
authors.initials: DR
authors.lastname: Sizemore
authors.forename: Lena
authors.initials: L
authors.lastname: Wehlin
authors.forename: Frank
authors.initials: F
authors.lastname: Weichold
authors.forename: Jan
authors.initials: J
authors.lastname: Andersson
authors.forename: Yasir A W
authors.initials: YA
authors.lastname: Skeiky
authors.forename: Jerry
authors.initials: J
authors.lastname: Sadoff
authors.forename: Hans
authors.initials: H
authors.lastname: Gaines
authors.forename: Rigmor
authors.initials: R
authors.lastname: Thorstensson
authors.forename: Mats
authors.initials: M
authors.lastname: Spångberg
authors.forename: Markus J
authors.initials: MJ
authors.lastname: Maeurer
mesh_terms: D000328:Adult; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007111:Immunity, Cellular; D015851:Interleukin-7 / Q000276:immunology; D008253:Macaca mulatta / Q000276:immunology*; D010766:Phosphorylation; D050799:STAT5 Transcription Factor / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055815:Young Adult
chemical_list: D016207:Cytokines; D015851:Interleukin-7; D050799:STAT5 Transcription Factor; D014409:Tumor Necrosis Factor-alpha
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