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

Abstract

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 IntroductionVertical transmission of HIV from an HIV-positive mother to her infant occurs in 15% to 25% of pregnancies if no precautions are taken. However, the risk of vertical transmission of HIV has been dramatically reduced with the introduction of antiretroviral treatment in combination with delivery by elective cesarean section and avoidance of breastfeeding. 1,2 Although infants of HIV-positive mothers are rarely HIVinfected, they may have been exposed to HIV proteins or even HIV particles during fetal life, as indicated by the presence of HIV-specific T cells, immune activation, and positive HIV polymerase chain reaction (PCR) found in HIV-exposed infants. [3][4][5][6][7] Thus, a recent study demonstrated high frequencies of HIV-specific CD4 ϩ cells and a lower frequency of HIV-specific CD8 ϩ cells, indicating transplacental diffusion of HIV-soluble proteins. 8 HIV particles as well as HIV proteins are known to inhibit progenitor cell function and to cause progenitor cell apoptosis which, in turn, would lead to both hematologic and immunologic deficiencies in the infants. [9][10][11][12][13][14][15][16][17][18] Furthermore, cytokine imbalance between Th1-and Th2-type cytokines has been suggested in HIV-positive individuals. [19][20][21] Such an imbalance in pregnant HIV-positive women might also cause cytokine imbalance in the fetus, resulting in immunologic deficiencies. Finally, pregnant HIV-positive women are commonly treated with antiretroviral therapy including zidovudine (AZT), and AZT is known to inhibit bone marrow functions. 22 The present study was conducted to determine if HIV-negative infants of HIV-positive mothers have immune deficiencies as determined by CD4 and CD8 counts in cord blood. Furthermore, thymic output was evaluated by determination of CD4 ϩ and CD8 ϩ cells with naive phenotype (coexpression of CD45RA) and determination of T-cell receptor excision circles (TRECs). Evidence of reduced thymic output was found and, to determine if impaired progenitor cell function might contribute to this, colony-forming cell (CFC) assays were performed to examine the function of myeloid progenitors, and fetal thymic organ cultures (FTOCs) were done to examine the function of T-cell progenitors. Recently, correlation between lymphocyte proliferation and expression of the early activation marker CD69 has been shown. 23,24 To determine if immune activation in infants of HIV-positive mothers might contribute to the lower level of naive CD4 ϩ cel...

Foxp3+CD4+CD25+ T cells control virus-specific memory T cells in chimpanzees that recovered from hepatitis C

“…Consistent with other publications 26,27,38 purified CD8 ϩ cells contained on average 3.1% CD4 ϩ cells (range, 0.6%-3.5%, with one exception of 6.2%). Irradiated CD4 Ϫ CD8 Ϫ cells or CD3-depleted PBMCs were used as autologous antigen-presenting cells (APCs).…”

Epidemiology of Acute Lower Respiratory Tract Infection in HIV-Exposed Uninfected Infants

“…7 This elevated mortality as well as the observed increased risks of hospitalization in our study may be the result of immunologic deficits that have been documented in HEU infants. [41][42][43][44] The degree of maternal immunosuppression has been shown to be an important predictor of infant survival, and ART use in pregnancy may have an impact on infant birth weight and immune response, but we did not have data on maternal CD4+ T-cell count or use of ART during pregnancy in our study to assess this association. 45,46 Other possible reasons for the increased risk of severe outcomes observed in HEU infants include possible increased exposure to maternally derived pathogens including cytomegalovirus, reduced transfer of protective antibodies from severely immunosuppressed mothers, and possible impaired responses to some vaccines.…”

Imbalance of naive and memory T lymphocytes with sustained high cellular activation during the first year of life from uninfected children born to HIV-1-infected mothers on HAART

“…However, Immune activation in HIV-exposed uninfected infants www.bjournal.com.br being conceived and undergoing embryonic and fetal development in an environment modified by maternal HIV infection can have consequences that might go beyond HIV infection itself. A limited number of studies have addressed this issue (4,5), highlighting the state of immune activation (4,6) in children born to HIV-infected mothers. However, in these studies, data were collected from children whose mothers had not necessarily received HAART, the currently accepted antenatal treatment for maternal HIV infection (3).…”