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...
To examine the impact of thymic size on immune recovery in patients with human immunodeficiency virus (HIV) infection, the thymus was visualized, using computed tomographic scans, in 25 HIV-infected patients who had received highly active antiretroviral therapy (HAART) for 6-18 months and had levels of viremia <500 copies/mL. For comparison, 10 control subjects were included in the study. Total and naive CD4+ cell counts were determined by flow cytometry. To determine thymic output, the number of CD4+ cells containing T cell receptor excision circles (TRECs) was measured. Qualitative immune recovery was evaluated by determination of CD4+ T cell receptor repertoire in 19 of the HIV-infected patients. Larger thymic size was associated with higher CD4+ cell counts (r=0.498; P=.011) and higher CD4+ TREC frequency (r=0.652; P<.001). Furthermore, patients with abundant thymic tissue seemed to have broader immunologic repertoires, compared with patients with minimal thymic tissue (P=.054). These findings suggest that thymopoiesis is ongoing in the adult thymus and contributes to immune reconstitution in HIV-infected patients receiving HAART.
This study evaluated the effect of highly active antiretroviral therapy (HAART)-induced viral suppression on T-cell receptor excisional circles (TRECs), telomere length, proliferative responses and spontaneous as well as phytohaemagglutinin (PHA)-stimulated lymphocyte apoptosis in 27 human immunodeficiency virus (HIV)-infected individuals followed for 18 months during HAART. Our results show that HAART significantly increased the level of TRECs in CD4 þ cells (P ¼ 0.003) after 18 months of almost continuously suppressed HIV-RNA levels. Lymphocyte proliferative responses and apoptosis levels in patients were significantly lower and significantly higher, respectively, compared with healthy controls. The proliferative response and apoptosis levels did not change during follow up. Changes in telomere length were observed in CD4 þ and in CD8 þ T cells. The study demonstrated that HAART induces normal TREC levels in the CD4 þ T-cell pool. However, the other perturbed functions in T cells indicate that immune reconstitution is incomplete and may need longer viral suppression.
In adult HIV-infected patients, thymic size evaluated from CT scans seems to be important to the degree of immune reconstitution obtainable during treatment with highly active antiretroviral therapy (HAART). To examine whether ultrasound is as reliable as CT for estimating thymic size and predicting immune recovery, CT and ultrasound scans were performed in 25 adult HIV-infected patients and 10 controls. CD4 counts and naive CD4 counts were measured in order to determine immune reconstitution. Furthermore, the CD4+ T-cell receptor excision circle (TREC) frequency and T-cell receptor (TCR) repertoire were determined. The study demonstrated no correlation between the 2 scanning methods (r = 0.201, p = 0.358 in patients and r = 0.457, p = 0.184 in controls). Among the patients, no association was found between the sonographically estimated thymic size and immunological parameters such as CD4 count (r = 0.083, p = 0.706), naive CD4 count (r = 0.067, p = 0.762), CD4 + TREC frequency (r = 0.028, p = 0.900) and CD4 + TCR repertoire (r = -0.057, p = 0.828). These findings show that CT remains superior for assessing thymic size in adults and is preferable to ultrasound when evaluating the importance of a large thymus to immune recovery during HAART.
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