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Blood, 15 July 2001, Vol. 98, No. 2, pp. 398-404
IMMUNOBIOLOGY
Impaired progenitor cell function in HIV-negative infants of
HIV-positive mothers results in decreased thymic output and low
CD4 counts
Susanne D. Nielsen,
Dorthe
L. Jeppesen,
Lilian Kolte,
Dawn R. Clark,
Tine U. Sørensen,
Anne-Mette Dreves,
Annette K. Ersbøll,
Lars P. Ryder,
Niels H. Valerius, and
Jens O. Nielsen
From the Department of Infectious Diseases and
Department of Pediatrics, Hvidovre Hospital, Hvidovre, Denmark; The
Netherlands Cancer Institute, Amsterdam, The Netherlands; the
Department of Immunology, Rigshospitalet, Copenhagen, Denmark; and the
Department of Animal Science and Animal Health, Royal Veterinary and
Agricultural University, Frederiksberg, Denmark.
Hematologic and immunologic functions were examined in 19 HIV-negative infants of HIV-positive mothers and 19 control infants of
HIV-negative mothers. Control infants were selected to match for
gestational age, weight, and mode of delivery. Cord blood was obtained
from all infants and used for flow cytometric determination of
lymphocyte subsets, including the naive CD4 count. Furthermore, to
determine thymic output, cord blood mononuclear cells were used for
determination of T-cell receptor excision circles (TRECs). Evaluation
of progenitor cell function was done by means of colony-forming cell
assay and fetal thymic organ cultures (FTOCs). Lower naive CD4 counts
(459.3 ± 68.9 vs 1128.9 ± 146.8 cells/µL,
P < .001) and reduced thymic output in infants of
HIV-positive mothers were found (frequency of CD4+
cells with TRECs was 3.6% ± 0.7% compared with 14.3% ± 2.2%
in controls, P < .001). In combination with lower red
blood cell counts in infants of HIV-positive mothers, this finding
suggested impairment of progenitor cell function. Indeed, progenitors
from infants of HIV-positive mothers had decreased cloning
efficiency (15.7% ± 2.6% vs 55.8% ± 15.9%,
P = .009) and seemed to generate fewer T cells in FTOCs.
In conclusion, lower numbers of naive CD4+ cells and
reduced thymic output in HIV-negative infants of HIV-positive mothers
may be due to impaired progenitor cell function.
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