Z Gastroenterol 2020; 58(01): e56
DOI: 10.1055/s-0039-3402257
Poster Visit Session V Viral Hepatitis and Immunology: Saturday, February 15, 2020, 11:00 am – 11:45 am, Lecture Hall P1
Georg Thieme Verlag KG Stuttgart · New York

Cytokine patterns of newly identified HEV-specific CD4 T cell epitope

B Csernalabics
1   University Hospital Freiburg, Department of Internal Medicine II, Freiburg, Germany
,
M Smits
1   University Hospital Freiburg, Department of Internal Medicine II, Freiburg, Germany
,
K Zoldan
1   University Hospital Freiburg, Department of Internal Medicine II, Freiburg, Germany
,
M Panning
2   University Hospital Freiburg, Institute of Virology II, Freiburg, Germany
,
C Neumann-Haefelin
1   University Hospital Freiburg, Department of Internal Medicine II, Freiburg, Germany
,
R Thimme
1   University Hospital Freiburg, Department of Internal Medicine II, Freiburg, Germany
,
T Boettler
1   University Hospital Freiburg, Department of Internal Medicine II, Freiburg, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
03 January 2020 (online)

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Background:

Although immunocompetent individuals are able to spontaneously clear Hepatitis E Virus (HEV) infection, it is now well accepted that the emerging antibody response does not necessarily protect from re-infection, suggesting a lack of long-lasting neutralizing antibody responses. However, the successful vaccination against genotype 1 in China demonstrates the possibility for long-term protection. Furthermore HEV causes chronic infection and cirrhosis in immunocompromised hosts. In our study we aim to elucidate how CD4 T cells, especially follicular T helper (Tfh) cells, are involved in protection from HEV, as this subset is specialized to support B cells to mount a long-lasting and high affinity antibody response.

Methods:

Therefore, HEV-specific CD4 T cell epitopes (genotype 3 as most common genotype in Europe) were predicted in silico using the IEDB analysis resource consensus tool. Cytokine production of HEV-specific CD4 T cells was analyzed by flow cytometry after antigen-specific expansion of PBMCs from 26 patients and healthy donors (HD) that resolved HEV (rHEV) infection. Neutralizing antibody titers are currently being analyzed.

Results:

We identified 21 novel MHC class II restricted HEV-specific CD4 T cell epitopes in 25 out of the 26 rHEV patients/HD. Furthermore, we confirmed 5 of 6 previously described epitopes. More importantly, the individual epitopes induced different cytokine patterns. Whereas for some peptides a strong induction of IFN-g, IL-2 and IL-21 was observed, others failed to induce IL-21 production demonstrating a diversification of CD4 T cell response depending on the epitope with some epitopes predominantly inducing a Tfh response. Moreover, broader and stronger CD4 T cell responses were observed in patients that resolved HEV infection within the last 6 month pointing to a time dependence of a sufficient response to HEV.

Discussion:

Our results give first insights into the role of HEV-specific CD4 T cells during and after HEV infection. To further investigate the determinants of protection we will correlate the neutralizing antibody response to identify correlations between the breadth and quality of the Tfh cell response and the neutralizing antibody titers.