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CD95 expression and apoptosis during pediatric HIV infection: early upregulation of CD95 expression
T W McCloskey1, N Oyaizu, S Bakshi
1Department of Pediatrics, North Shore University Hospital-New York University School of Medicine, Manhasset 11030, USA.
Insights
Pediatric HIV infection accelerates immune decline. Early CD95 antigen expression on T cells in infants with pediatric HIV may precede apoptosis, impacting disease progression.
Area of Science:
- Immunology
- Pediatric Infectious Diseases
- Cell Biology
Background:
- Pediatric HIV infection leads to rapid CD4 T lymphocyte decline and immune dysfunction.
- Apoptosis, potentially via CD95 antigen, is a proposed mechanism for T cell loss in HIV.
- Disease progression is generally faster in children than in adults with HIV.
Purpose of the Study:
- To investigate CD95 expression and apoptosis in pediatric HIV infection.
- To correlate CD95 expression and apoptosis with immunologic categories in HIV-infected children.
- To determine the timing of CD95 upregulation in relation to apoptosis in infants with perinatally acquired HIV.
Main Methods:
- Analysis of peripheral blood lymphocytes from HIV-infected children across CDC immunologic categories.
- Flow cytometry to quantify CD95 expression on CD4 and CD8 T cells.
- Assessment of lymphocyte apoptosis rates.
Main Results:
- Increased percentages of CD95-expressing CD4/CD8 T cells and apoptotic lymphocytes were observed in HIV-infected children.
- Higher CD95 expression and apoptosis rates were found in immunologic Category III compared to Category I.
- Elevated CD95 expression was detected as early as 3 months of age, preceding increased apoptosis.
Conclusions:
- HIV-infected infants show early CD95 upregulation, even before significant apoptosis.
- This early CD95 expression aberration may play a critical role in the pathogenesis of perinatally acquired HIV disease.
- Findings suggest CD95 may be an early indicator of immune dysregulation in pediatric HIV.
Abstract:
Pediatric HIV infection is characterized by a progressive decline in CD4 T lymphocytes and faster disease progression than is typically seen in adults. Apoptosis, possibly mediated through the CD95 antigen, has been proposed as a mechanism for cell loss which eventually leads to immune dysfunction. In this study of peripheral blood lymphocytes from HIV-infected children, classified according to CDC immunologic categories, we found that the percentage of CD4 and CD8 T cells expressing CD95 and the percentage of lymphocytes undergoing apoptosis were increased in children with HIV infection and were greater in children from immunologic Category III as compared to those in Category I. Most striking was our observation that an increased percentage of CD95-positive cells appeared as early as 3 months of age, at a time when these children did not have elevated levels of apoptosis. These data demonstrate early upregulation of CD95 expression in HIV-infected infants, an abberation which may have profound implications for the pathogenesis of perinatally acquired HIV disease.