Impaired progenitor cell function in HIV-negative infants of HIV-positive mothers results in decreased thymic output and low CD4 counts

Hematologic and immunologic functions were examined in 19 HIV-negative infa nts of HIV-positive mothers and 19 control infants of HIV-negative mothers. Control infants were selected to match for gestational age, weight, and mo de of delivery. Cord blood was obtained from all infants and used for flow cytometric determination of lymphocyte subsets, including the naive CD4 cou nt. Furthermore, to determine thymic output, cord blood mononuclear cells w ere used for determination of T-cell receptor excision circles (TRECs), Eva luation of progenitor cell function was done by means of colony-forming cel l assay and fetal thymic organ cultures (FTOCs), Lower naive CD4 counts (45 9.3 +/- 68.9 vs 1128.9 +/- 146.8 cells/muL, P < .001) and reduced thymic ou tput in infants of HIV-positive mothers were found (frequency of CD4(+) cel ls 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 fun ction, Indeed, progenitors from infants of HIV-positive mothers had decreas ed cloning efficiency (15.7% +/- 2.6% vs 55.8% +/- 15.9%, P = .009) and see med to generate fewer T cells in FTOCs. In conclusion, lower numbers of nai ve CD4(+) cells and reduced thymic output in HIV-negative infants of HIV-po sitive mothers may be due to impaired progenitor cell function. (C) 2001 by The American Society of Hematology.