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. 2022 Jul 1;132(13):e148826.
doi: 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  2   3 , Anna-Ursula Happel  1 , Angela A Hoffmann  1 , Sami B Kanaan  4 , J Lee Nelson  4 , Clive M Gray  1 , Heather B Jaspan  1   2   5   6 , Whitney E Harrington  2   5
Affiliations

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

Christina Balle et al. J Clin Invest. .

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 that influence MMc detection and level across infancy and the effect of MMc on T cell responses to bacillus Calmette-Guérin (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 1, 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 to 1,193/100,000 genomic equivalents and was positively impacted by absence of maternal HIV, maternal and infant HLA compatibility, infant female sex, and exclusive breastfeeding. Initiation of maternal antiretroviral therapy prior to pregnancy partially restored MMc level 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 the level of MMc, which may subsequently affect infant T cell responses.

Keywords: AIDS/HIV; Bacterial vaccines; Immunology; Obstetrics/gynecology; T cells.

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Conflict of interest statement

Conflict of interest: SBK and JLN are cofounders of Chimerocyte, Inc. that develops highly sensitive chimerism analysis technologies. Chimerocyte, Inc. had no role in funding this research project.

Figures

Figure 1
Figure 1. Maternal microchimerism is dynamic and persists throughout infancy.
Maternal microchimerism (MMc) expressed as microchimeric equivalents per infant genomic equivalents (gEq) assessed. ND, not detected. (A) Proportion of infants with detectable MMc at birth (n = 58), week 7 (n = 55), week 15 (n = 53), and week 36 (n = 53) of life. (B) Quantitative levels of MMc across infancy. (C) Within-infant MMc kinetics. The dotted lines highlight MMc levels above 10/100,000 gEq (high) and above 100/100,000 gEq (very high).
Figure 2
Figure 2. Maternal microchimerism across infancy is associated with HIV exposure, maternal and infant HLA class II compatibility, and infant sex.
Maternal microchimerism (MMc) expressed as microchimeric equivalents per infant genomic equivalents (gEq) assessed. ND, not detected; iHU, HIV-unexposed infants; iHEU, HIV-exposed, uninfected infants. Detection of MMc in infants at day 1, week 7, week 15, and week 36 of life by (A) HIV exposure, (C) maternal and infant HLA class II compatibility (score indicates the number of shared alleles from the mother’s perspective), and (E) infant sex. Level of MMc across infancy by (B) HIV exposure, (D) maternal and infant HLA compatibility, and (F) infant sex.
Figure 3
Figure 3. Maternal microchimerism across infancy is associated with mode of feeding.
Maternal microchimerism (MMc) expressed as microchimeric equivalents per infant genomic equivalents (gEq) assessed. ND, not detected; EBF, exclusively breastfed; NBF, nonexclusively breastfed. (A) Detection of MMc in infants at day 1, week 7, and week 15 of life by mode of feeding. (B) Level of MMc across infancy by mode of feeding.
Figure 4
Figure 4. Maternal microchimerism across infancy is associated with duration of maternal antiretroviral therapy (ART).
Maternal microchimerism (MMc) expressed as microchimeric equivalents per infant genomic equivalents (gEq) assessed. ND, not detected; iHU, HIV-unexposed infants; early ART, HIV-exposed, uninfected infants whose mothers were on ART before conception; late ART, HIV-exposed, uninfected infants whose mothers initiated ART during pregnancy. (A) Detection of MMc in infants at day 1, week 7, week 15, and week 36 of life by HIV exposure and duration of ART. (B) Level of MMc across infancy by HIV exposure and duration of ART.
Figure 5
Figure 5. Maternal microchimerism at birth is positively associated with T cell responses to BCG vaccination.
(A) Polyfunctionality score (PFS) at week 7 and week 15 of life by detection of maternal microchimerism (MMc) at birth (N = no [purple], Y = yes [red]). (B) Association between PFS at week 7 (light green) and week 15 (green) of life and level of MMc per 100,000 genomic equivalents (gEq) at birth. Delta represents the adjusted effect size per 10/100,000 gEq. (C) PFS at week 7 and week 15 of life by detection of MMc at the concurrent time point (N = no [purple], Y = yes [red]). (D) Association between PFS at week 7 (light green) and week 15 (green) of life and level of MMc per 100,000 gEq at the concurrent time point. Delta represents the adjusted effect size per 10/100,000 gEq. Horizontal black lines in A and C indicate mean values, and black lines in B and D indicate best fit lines.
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