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Impaired T cell proliferation in acute dengue infection
1Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical Center, Worcester 01655, USA.
Abstract:
Decreased proliferative responses to mitogens and recall Ags have been observed in PBMC obtained during several acute human viral infections. To determine whether cell-mediated responses are altered during acute dengue infection, we examined the proliferative responses of PBMC from children enrolled in a prospective study of dengue infections in Thailand. All responses of PBMC during acute illness were compared with the same patients' PBMC obtained at least 6 mo after their infection. Proliferative responses to PHA, anti-CD3, tetanus toxoid, and dengue Ags were decreased significantly in PBMC obtained during the acute infection. The proliferative responses to PHA were restored by the addition of gamma-irradiated autologous convalescent or allogeneic PBMC. Cell contact with the irradiated PBMC was necessary to restore proliferation. Non-T cells from the acute PBMC of dengue patients did not support proliferation of T cells from control donors in response to PHA, but T cells from the PBMC of patients with acute dengue proliferated if accessory cells from a control donor were present. Addition of anti-CD28 Abs restored anti-CD3-induced proliferation of the PBMC of some patients. The percentage of monocytes was reduced in the acute sample of PBMC of the dengue patients. Addition of IL-2 or IL-7, but not IL-4 or IL-12, also restored proliferation of acute PBMC stimulated with anti-CD3. The results demonstrate that both quantitative and qualitative defects in the accessory cell population during acute dengue illness result in a depression of in vitro T cell proliferation.
Insights
During acute dengue infection, T cell proliferation is suppressed due to defects in accessory cells. Restoring cell contact or adding specific cytokines can improve these immune responses in dengue patients.
Area of Science:
- Immunology
- Virology
- Cellular Biology
Background:
- Acute viral infections often impair peripheral blood mononuclear cell (PBMC) responses to mitogens and antigens.
- Cell-mediated immunity plays a crucial role in controlling viral infections, but its status during dengue fever is not fully understood.
Purpose of the Study:
- To investigate alterations in cell-mediated immune responses, specifically T cell proliferation, during acute dengue infection.
- To identify the underlying cellular and molecular mechanisms responsible for impaired T cell responses in dengue patients.
Main Methods:
- Prospective study of children with dengue infection in Thailand.
- Comparison of PBMC proliferative responses to phytohemagglutinin (PHA), anti-CD3, tetanus toxoid, and dengue antigens during acute illness versus convalescence.
- In vitro experiments involving co-culture with irradiated PBMC, addition of antibodies (anti-CD28), cytokines (IL-2, IL-7, IL-4, IL-12), and assessment of monocyte percentages.
Main Results:
- PBMC from patients during acute dengue showed significantly decreased proliferative responses to various stimuli compared to convalescent samples.
- T cell proliferation was restored by cell contact with irradiated PBMC and by adding IL-2 or IL-7, suggesting accessory cell dysfunction.
- Reduced monocyte percentages and impaired accessory cell function were observed in acute dengue PBMC, impacting T cell activation.
Conclusions:
- Acute dengue infection leads to significant depression of in vitro T cell proliferation.
- Both quantitative (reduced monocytes) and qualitative defects in accessory cells contribute to impaired T cell responses during dengue.
- Understanding these immune defects is crucial for developing therapeutic strategies against dengue.