No abstract

The objective of this research was to investigate if breastfeeding affects the size of the thymus. Ultrasound assessment of the thymic index (a volume estimate) at birth and age 4 months in 47 healthy infants born in the hospital were used. History of feeding mode, body size and illness were registered. At 4 months the geometric mean thymic index (range) was 38.3 (16.2-83.2) in exclusively breastfed infants (n = 21), 27.3 (15.6-50.0) in partially breastfed infants (n = 13) and 18.3 (12.2-32.6) in formula fed infants (n = 13; p = 0.0001, ANOVA). This finding was independent of weight, length, sex and previous or current illness. There was no significant difference in mean thymic index at birth between the three feeding groups and mean thymic index had increased in all three groups from birth to 4 months. For the formula-fed infants it seems that the thymus remains large for a period and then decreases in size after breastfeeding has been terminated. We conclude that the thymus is considerably larger in breastfed than in formula-fed infants at the age of 4 months. The cause of this difference is unknown but human milk contains many immune modulating factors that might cause this effect.

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.