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Cytokine patterns during progression to AIDS in children with perinatal HIV infection
E Hyjek1, H W Lischner, T Hyslop
1Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Insights
Cytokine profiles in children with perinatal HIV infection show reduced IL-2 and increased IL-4, IL-10, and IFN-gamma with disease progression. This suggests a shift towards Th2 responses impacting immunodeficiency.
Area of Science:
- Immunology
- Virology
- Pediatrics
Background:
- Perinatal HIV infection significantly impacts the developing immune system.
- Cytokine expression patterns are crucial indicators of immune status in HIV-infected children.
Purpose of the Study:
- To analyze cytokine expression patterns in response to polyclonal and antigenic stimuli in children with perinatal HIV infection.
- To investigate the relationship between cytokine profiles, disease stage, and immune cell populations.
Main Methods:
- Analysis of peripheral blood mononuclear cells (PBMC) and peripheral blood lymphocytes (PBL) from HIV-infected and uninfected children.
- Stimulation of cells with phorbol 12-myristate 13-acetate (PMA), calcium ionophore A23187, phytohemagglutinin (PHA), HLA alloantigens, HIV peptides, and tetanus toxoid.
- Measurement of cytokine levels including IL-2, IL-4, IL-5, IL-10, and IFN-gamma.
Main Results:
- HIV-infected children showed reduced IL-2 and increased IL-4, IL-10, and IFN-gamma with age and disease progression.
- Cytokine levels generally did not differ significantly between HIV-infected and uninfected children, except for a reduction in late-stage infection.
- Children with poor antigenic responses had lower CD4+ counts and a distinct cytokine profile (higher IL-4/IL-5, lower IL-2/IFN-gamma) upon PHA stimulation.
Conclusions:
- Cytokine expression in HIV-infected children is stimulus-dependent and linked to PBMC phenotype.
- A shift towards T-helper 2 (Th2) antigen-specific responses may prevail during HIV-induced immunodeficiency progression.
Abstract:
Patterns of cytokine expression were analyzed in polyclonal and antigenic responses in children with perinatal HIV infection. Responses of PBL to PMA and A23187 calcium ionophore studied in patients in different stages of HIV infection revealed reduced levels of IL-2 in HIV-infected children beginning before 6 mo of age, and age-dependent increases in expression of IL-4, IL-10, and IFN-gamma. The levels of IL-4, IL-10, and IFN-gamma expression did not differ significantly between HIV-infected and age-matched uninfected children of HIV-seropositive mothers, except for a small reduction in HIV-infected children in late stages of infection. Responses to PHA, HLA alloantigens, HIV envelope peptides T1 and P18, and tetanus toxoid were studied in PBMC derived from asymptomatic and mildly symptomatic HIV-infected children. IL-2, IFN-gamma, IL-4, and IL-5 expression was detected in PHA-stimulated PBMC from all analyzed patients. HIV-infected children who failed to respond to HLA alloantigens, tetanus toxoid, or the envelope peptides had lower numbers of CD4+ cells and expressed, on PHA stimulation, higher levels of IL-4 and IL-5 and lower levels of IL-2 and IFN-gamma than patients who responded to the antigenic stimulation. Results of these analyses suggest that cytokine expression in HIV-infected children depends on the character of the stimuli as well as the phenotype of PBMC, and indicate possible prevalence of Th2 Ag-specific responses during the progression of HIV-induced immunodeficiency.