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Impeded Th1 CD4 memory T cell generation in chronic-persisting liver infection with Echinococcus multilocularis
Burkhard J Manfras1, Stefan Reuter, Thomas Wendland
1Division of Infectious Diseases and Clinical Immunology, Department of Internal Medicine, University of Ulm, Robert-Koch-Strasse 8, 89081 Ulm, Germany. burkhard.manfras@medizin.uni-ulm.de
International Immunology
|December 23, 2003
Summary
Echinococcus multilocularis infection leads to low levels of specific CD4(+) T cells producing T(h)1 cytokines, indicating impaired cellular immunity. This hyporesponsiveness is specific to the parasite and differs from responses to other pathogens.
Area of Science:
- Immunology
- Parasitology
- Cellular Immunity
Background:
- CD4(+) T cells are crucial for coordinating immune responses through cytokine secretion.
- The role of adaptive cellular immunity in Echinococcus multilocularis infection is not well understood.
- Efficacy of immune responses depends on memory T cell numbers and cytokine profiles.
Purpose of the Study:
- To investigate immunological memory in patients with alveolar echinococcosis (AE).
- To determine the extent of cellular immunity induced by Echinococcus multilocularis infection.
- To analyze the cytokine secretion profile of CD4(+) T cells in AE patients.
Main Methods:
- Peripheral lymphocytes from AE patients were studied ex vivo.
- Cells were stimulated with E. multilocularis antigen, recall antigen, and phytohemagglutinin.
- Cytokine production (IFN-gamma, IL-2, TNF-alpha, IL-4, IL-5, IL-10) was measured using flow cytometry and ELISPOT.
Main Results:
- Frequencies of E. multilocularis-specific CD4(+) T cells producing T(h)1 cytokines were low in chronic AE (mean 0.5%).
- A majority of AE patients (68%) showed a detectable E. multilocularis-specific CD4(+) T cell response (>/=0.1%).
- Low T(h)1 cytokine-secreting cells were observed in active and inactive disease, and not increased in cured patients.
Conclusions:
- Antigen-specific memory function against E. multilocularis is distinct from responses to viral or bacterial pathogens.
- A specific hyporesponsiveness of CD4(+) memory T cells occurs during chronic helminth infection.
- It remains undetermined if this hyporesponsiveness causes or results from metacestode activity.