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Abnormal CD40 ligand (CD154) expression in human immunodeficiency virus-infected children
M R O'Gorman1, B DuChateau, M Paniagua
1Children's Memorial Hospital and the Northwestern University Medical School, Chicago, Illinois 60614-3394, USA. mogorman@nwu.edu
Insights
Pediatric HIV infection impairs T helper cell CD154 expression, affecting immune responses. This CD40 ligand deficiency correlates with immunodeficiency but not viral load in children.
Area of Science:
- Immunology
- Virology
- Pediatrics
Background:
- CD40 ligand (CD154) is crucial for B-cell function and immunoglobulin class switching.
- Pediatric HIV infection is characterized by early B-cell abnormalities and immune dysregulation.
- CD154 expression on T helper cells plays a key role in adaptive immunity.
Purpose of the Study:
- To investigate CD154 expression levels on T helper cells in HIV-infected children.
- To compare CD154 expression in HIV-infected children with uninfected controls.
- To determine the correlation between CD154 expression and clinical parameters in pediatric HIV infection.
Main Methods:
- Flow cytometry was used to measure CD154 expression on T helper cells (CD3(+) CD8(-)).
- Measurements were taken on resting and in vitro-activated T helper cells.
- Correlations were analyzed between CD154 levels, CD4 T-cell counts, viral load, and immunoglobulin concentrations.
Main Results:
- HIV-infected children showed significantly lower percentages and mean fluorescence channel (MFC) of activated CD154+ T helper cells compared to controls.
- CD154 expression on resting T helper cells did not differ significantly between groups.
- Activated CD154 expression correlated with CD4 T-cell levels (r=0.707, P=0.003) and baseline immunoglobulin A levels in HIV-infected children.
Conclusions:
- HIV-infected children exhibit impaired regulation of CD154 expression on activated T helper cells.
- This CD154 deficiency may contribute to the immune dysregulation observed in pediatric HIV infection.
- Further research is warranted to explore therapeutic strategies targeting CD154 in pediatric HIV.
Abstract:
The CD40 ligand (CD154), expressed primarily on activated CD4-positive T cells, is a costimulatory molecule involved in B-cell proliferation, germinal center formation, and immunoglobulin class switching. Since B-cell abnormalities including hypergammaglobulinemia and abnormal antibody-specific immune responses are prominent and occur early during the course of pediatric human immunodeficiency virus (HIV) infection, we measured the baseline levels and the induced levels of expression of CD154 on CD3(+) CD8(-) (T helper cells) in HIV-infected children and uninfected children born to HIV-positive mothers. The percentage of CD154(+) T helper cells activated in vitro and the level of CD154 expressed per T helper cell (mean fluorescent channel [MFC]) were significantly lower in the HIV-infected children than in the uninfected control group (77% +/- 3% versus 89% +/- 1%, respectively [P < 0.002], and 261 +/- 174 versus 415 +/- 130 MFC, respectively [P < 0.03]). The levels of CD154 expressed on resting T helper cells in the HIV-infected group were not significantly different from the levels observed in the control group. In the HIV-infected children, the level of CD154 on activated T helper cells correlated with the level of immunodeficiency, as assessed by the CD4 T-cell levels (correlation coefficient [r] = 0.707, P = 0.003), but did not correlate with the viral load or with any of the serum immunoglobulin concentrations measured in this group of HIV-infected children. The baseline level of CD154 expressed on T helper cells did, however, correlate with the concentration of immunoglobulin A in serum. We conclude that HIV-infected children have impaired regulation of CD154 expression which may contribute to the immune dysregulation commonly observed.
