Perinatal transmission of human immunodeficiency virus type 1 (HIV-1) accounts for most new cases of pediatric AIDS in the United States. Disease progression is rapid compared to individuals infected later in life. Maternal factors, such as viral load, total CD4+ T cells and viral tropism, affect the rate of vertical transmission of HIV-1. The influence of the fetal immune system on viral transmission is poorly understood. T-cell tropic HIV-1 strains, the predominant viral subset associated with later stages of infection, are associated with decreased CD4+ cells and progression to AIDS. Our hypothesis is that cord blood CD4+ T lymphocytes express CXCR4, co-receptor for T-cell tropic strains, rather than CCR5, co-receptor for macrophage-tropic viral subsets. We studied 8 cord blood samples from HIV-negative pregnancies and 8 peripheral blood samples from HIV-negative adult volunteers. Peripheral blood mononuclear cells and cord blood mononuclear cells were separated from whole blood using Ficoll/Hypaque solution. CD4+ cells were selected using MACS CD4 Microbeads. Total RNA was isolated from 1 × 106 CD4+ cells from each sample; RNA was reverse transcribed with random primers. An aliquot of each reaction was amplified by polymerase chain reaction using oligonucleotide primers specific for CCR5 and CXCR4. Primers for glyceraldehyde 3-phosphodehydrogenase were included in each reaction to normalize the amount of co-receptor mRNA expressed. Amplification products were separated by polyacrylamide gel electrophoresis which was analyzed and the signal quantified on a PhosphorImager. We found that CD4+ cells from cord blood samples express 3 times the amount of CXCR4 mRNA as adult CD4+ cells (18±6 vs 6±2; p<0.001). The expression of CCR5 mRNA was less in cord blood compared to adults (0.9±0.1 vs 0.4±0.2; p<0.001). These results support our hypothesis that cord blood CD4+ cells express the T-tropic HIV-1 strain co-receptor CXCR4 in greater amounts than the macrophage-tropic strain co-receptor CCR5. We speculate that fetal T lymphocytes are more susceptible to infection by T-cell tropic viral strains which contributes to the rapid progression to AIDS in children infected during the perinatal period. We also speculate that the relative lack of CCR5 may be protective to the fetus when the mother transmits macrophage-tropic strains.
Author information
Authors and Affiliations
Additional information
(Spon by: Cynthia T. Barrett)
Rights and permissions
About this article
Cite this article
Mark, D., Yue, X. & Gray, S. Cord Blood CD4+ T Lymphocytes Differentially Express CCR5 and CXCR4, HIV-1 Co-receptors † 1404. Pediatr Res 43 (Suppl 4), 240 (1998). https://doi.org/10.1203/00006450-199804001-01425
Issue Date:
DOI: https://doi.org/10.1203/00006450-199804001-01425