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Change history

  • 12 October 2018

    In this Brief Communications Arising Comment, the first three authors (Osuna, Lim and Kublin) should have been listed as equally contributing authors; this has been corrected online.

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Author information

Author notes

  1. These authors contributed equally: Christa E. Osuna, So-Yon Lim, Jessica L. Kublin.

Affiliations

  1. Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

    • Christa E. Osuna
    • , So-Yon Lim
    • , Jessica L. Kublin
    • , Elsa Chen
    •  & James B. Whitney
  2. Center for Human Immunology, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA

    • Richard Apps
  3. Division of Infectious Diseases, Weill Department of Medicine, Weill Cornell Medical College, New York, NY, USA

    • Talia M. Mota
    • , Szu-Han Huang
    • , Yanqin Ren
    • , Nathaniel D. Bachtel
    • , R. Brad Jones
    •  & Douglas F. Nixon
  4. Brigham and Women’s Hospital, Boston, Massachusetts Harvard Medical School, Boston, MA, USA

    • Athe M. Tsibris
  5. Thayer School of Engineering, Dartmouth College, Hanover, NH, USA

    • Margaret E. Ackerman
  6. Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA

    • James B. Whitney

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Contributions

D.F.N. and J.B.W. designed the studies. R.B.J., R.A., E.C., Y.R., N.D.B., C.E.O., R.T. and S.Y.L. led the virology assays. S.H.H., D.C., J.L.K., M.A. and C.E.O. led the immunology assays. J.B.W. led the studies and wrote the paper with all co-authors.

Competing interests

Declared none.

Corresponding author

Correspondence to James B. Whitney.

Extended data figures and tables

  1. Extended Data Fig. 1 Frequency and activation status of CD32-expressing CD4+ T cells and their HIV-1 DNA content.

    a, The frequency of CD32high CD4+ T cells was measured by flow cytometry in PBMCs from ART-suppressed, HIV-1+ (n = 20) and HIV-1 (n = 8) donors. Bars denote median values. P values were determined by a Mann–Whitney test. b, DNA copies per cell in sorted subsets of total CD4+, CD4+CD32neg, CD4+CD32int and CD4+CD32high T cells are shown with median values and the IQR. The results are shown as either the actual HIV-1 DNA copies per million cells (filled symbols) or as estimated values calculated using the LOD and applied to the number of cells when the DNA input did not reach the threshold (open symbols). P values were determined by a Kruskal–Wallis test. c, The percentage of CD69, CD25 and HLA-DR expression was measured by flow cytometry on CD32neg and CD32high (FUN-2) CD4+ T cells from PBMCs from HIV-1+ participants (n = 20). Error bars show the median and IQR. P values were determined by Wilcoxon matched-pairs signed rank tests.

  2. Extended Data Fig. 2 Detection of B cell proteins and mRNA in CD32-expressing CD4+ T cells.

    a, CD32neg and CD32high (FUN-2) CD4+ T cells from human PBMCs were assessed by flow cytometry for the expression of CD19, CD40 and HLA-DR, and compared to B cells (CD3 CD14CD19+ lymphocytes). Representative flow cytometry results of per cell antigen levels on B cells (top, blue histograms) and CD32neg and CD32high CD4+ T cells (bottom, grey and red histograms, respectively) from an HIV-1 donor. b, Representative CD32b staining of PBMCs from an HIV-1+, ART-suppressed participant. PBMCs were stained with an optimized concentration of the 2B6 monoclonal anti-CD32b antibody, followed by an antibody cocktail that included the FUN-2 monoclonal pan-CD32 antibody, as described in the Methods. Shown are the 2B6 and FUN-2 fluorescence minus one (FMO) antibody cocktail-stained samples and a sample co-stained with 2B6 and FUN-2. c, d, CD32 mRNA expression levels in CD4+CD32+ subsets. c, The relative expression of CD32A and CD32B mRNA isoforms in sorted CD4+CD32int and CD4+CD32high subsets from HIV-1+, ART-suppressed participants (n = 4). d, mRNA expression of CD32A and CD32B from patient G07W1610. e, T and B cell lineage-specific mRNA transcripts in sorted CD4+CD32+ subsets from participant G07W1610. Relative mRNA expression of target genes was normalized to ATCB using the comparative Ct method. Results are mean ± s.d. of each value from each participant (n = 4; c), or from values generated from two separate experiments using samples from the same patient (d).

  3. Extended Data Fig. 3 Doublet composition of the sorted CD4+CD32high T cells.

    Sorted B cells and CD4+CD32neg, CD4+CD32int and CD4+CD32high T cells from an HIV-1+, ART-suppressed participant were analysed using an Amnis imaging cytometer. Singlets and doublets were quantified using the aspect ratio and nuclear staining. a, The proportion of total singlet and doublet events among total nucleated cells detected on the Amnis cytometer in each sorted population was determined, and is shown as individual composite bar graphs for two patients (G07W1610 and OM5365). b, A composite bar graph of the proportion of conjugates, doublets and trogocytotic events that comprised the sorted CD4+CD32high population (n = 2).

  4. Extended Data Table 1 Viral suppression of 20 HIV-1-infected participants on ART
  5. Extended Data Table 2 CD4+CD32high subset proportions and HIV-1 DNA compared to total CD4+ and CD32neg CD4+ T cells

Supplementary information

  1. Supplementary Information

    This file contains Supplementary Figure 1, Supplementary Methods and Supplementary References.

  2. Reporting Summary

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DOI

https://doi.org/10.1038/s41586-018-0495-2

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