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ResearchIn-Press PreviewAIDS/HIVImmunology Open Access | 10.1172/JCI148826

Factors influencing maternal microchimerism throughout infancy and its impact on infant T cell immunity

Christina Balle,1 Blair Armistead,2 Agano Kiravu,1 Xiaochang Song,3 Anna-Ursula Happel,1 Angela A. Hoffmann,1 Sami B. Kanaan,4 J. Lee Nelson,4 Clive M. Gray,1 Heather B. Jaspan,5 and Whitney E. Harrington5

1Department of Pathology, University of Cape Town, Cape Town, South Africa

2Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, United States of America

3School of Medicine, University of Washington, Seattle, United States of America

4Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America

5Department of Pediatrics, University of Washington and Seattle Children's Research Institute, Seattle, United States of America

Find articles by Balle, C. in: JCI | PubMed | Google Scholar |

1Department of Pathology, University of Cape Town, Cape Town, South Africa

2Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, United States of America

3School of Medicine, University of Washington, Seattle, United States of America

4Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America

5Department of Pediatrics, University of Washington and Seattle Children's Research Institute, Seattle, United States of America

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1Department of Pathology, University of Cape Town, Cape Town, South Africa

2Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, United States of America

3School of Medicine, University of Washington, Seattle, United States of America

4Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America

5Department of Pediatrics, University of Washington and Seattle Children's Research Institute, Seattle, United States of America

Find articles by Kiravu, A. in: JCI | PubMed | Google Scholar |

1Department of Pathology, University of Cape Town, Cape Town, South Africa

2Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, United States of America

3School of Medicine, University of Washington, Seattle, United States of America

4Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America

5Department of Pediatrics, University of Washington and Seattle Children's Research Institute, Seattle, United States of America

Find articles by Song, X. in: JCI | PubMed | Google Scholar

1Department of Pathology, University of Cape Town, Cape Town, South Africa

2Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, United States of America

3School of Medicine, University of Washington, Seattle, United States of America

4Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America

5Department of Pediatrics, University of Washington and Seattle Children's Research Institute, Seattle, United States of America

Find articles by Happel, A. in: JCI | PubMed | Google Scholar

1Department of Pathology, University of Cape Town, Cape Town, South Africa

2Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, United States of America

3School of Medicine, University of Washington, Seattle, United States of America

4Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America

5Department of Pediatrics, University of Washington and Seattle Children's Research Institute, Seattle, United States of America

Find articles by Hoffmann, A. in: JCI | PubMed | Google Scholar

1Department of Pathology, University of Cape Town, Cape Town, South Africa

2Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, United States of America

3School of Medicine, University of Washington, Seattle, United States of America

4Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America

5Department of Pediatrics, University of Washington and Seattle Children's Research Institute, Seattle, United States of America

Find articles by Kanaan, S. in: JCI | PubMed | Google Scholar

1Department of Pathology, University of Cape Town, Cape Town, South Africa

2Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, United States of America

3School of Medicine, University of Washington, Seattle, United States of America

4Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America

5Department of Pediatrics, University of Washington and Seattle Children's Research Institute, Seattle, United States of America

Find articles by Nelson, J. in: JCI | PubMed | Google Scholar

1Department of Pathology, University of Cape Town, Cape Town, South Africa

2Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, United States of America

3School of Medicine, University of Washington, Seattle, United States of America

4Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America

5Department of Pediatrics, University of Washington and Seattle Children's Research Institute, Seattle, United States of America

Find articles by Gray, C. in: JCI | PubMed | Google Scholar |

1Department of Pathology, University of Cape Town, Cape Town, South Africa

2Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, United States of America

3School of Medicine, University of Washington, Seattle, United States of America

4Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America

5Department of Pediatrics, University of Washington and Seattle Children's Research Institute, Seattle, United States of America

Find articles by Jaspan, H. in: JCI | PubMed | Google Scholar

1Department of Pathology, University of Cape Town, Cape Town, South Africa

2Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, United States of America

3School of Medicine, University of Washington, Seattle, United States of America

4Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, United States of America

5Department of Pediatrics, University of Washington and Seattle Children's Research Institute, Seattle, United States of America

Find articles by Harrington, W. in: JCI | PubMed | Google Scholar |

Published May 12, 2022 - More info

J Clin Invest. https://doi.org/10.1172/JCI148826.
Copyright © 2022, Balle et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published May 12, 2022 - Version history
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Abstract

Determinants of the acquisition and maintenance of maternal microchimerism (MMc) during infancy and the impact of MMc on infant immune responses are unknown. We examined factors which influence MMc detection and level across infancy and the effect of MMc on T cell responses to BCG vaccination in a cohort of HIV exposed, uninfected and HIV unexposed infants in South Africa. MMc was measured in whole blood from 58 infants using a panel of quantitative PCR assays at day one and 7, 15, and 36 weeks of life. Infants received BCG at birth, and selected whole blood samples from infancy were stimulated in vitro with BCG and assessed for polyfunctional CD4+ T cell responses. MMc was present in most infants across infancy with levels ranging from 0-1,193/100,000 genomic equivalents and was positively impacted by absence of maternal HIV, maternal-infant HLA compatibility, infant female sex, and exclusive breastfeeding. Initiation of maternal antiretroviral therapy prior to pregnancy partially restored MMc levels in HIV exposed, uninfected infants. Birth MMc was associated with an improved polyfunctional CD4+ T cell response to BCG. These data emphasize that both maternal and infant factors influence MMc, which may subsequently impact infant T cell responses.

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