Protective cross-reactive T cell response in chronic lymphocytic choromeningitis virus infection upon Pichinde virus challenge

Mischke, J.; Klein, S.; Prinz, I.; Cornberg, M.; Kraft, ARM

Immunological memory to a previously encountered pathogen can influence the outcome of an infection with an unrelated pathogen, so called heterologous immunity. Lymphocytic choromeningitis virus (LCMV) immune mice sequentially infected with Pichinde virus (PICV) resulted in a protective cross-reactive NP205-specific T cell response. So far, limited data are available how cross-reactive T cell responses behave in chronic infections with exhausted T cell responses and how checkpoint inhibitor therapy might affect these responses. The aim of this study was to investigate the influence of heterologous immunity in chronic LCMV clone 13 (LCMVcl13) infections with and without checkpoint inhibitor therapy after PICV infection on a phenotypical, functional and T cell receptor (TCR) level. A protective immune response against a primary PICV infection was detectable in chronically LCMV infected mice similar to LCMV-immune mice. This was also mediated by IFNγ+ cross-reactive NP205-specific CD8+ T cells. Although an altered phenotype of NP205-specific T cells was detectable, no major differences in the clonality and diversity of their TCR repertoire were observed. Despite the lower number of cross-reactive NP205 responses, the chronically infected mice were protected from PICV mediated weight loss compared to naive PICV infected mice. Checkpoint inhibitor treatment with αPD-L1 had no major effect in terms of immune response against sequential PICV infection. Our study demonstrated that cross-reactive CD8+ T cells also exist in the setting of chronic infection and are capable of responding to sequential PICV infection, albeit in an attenuated form, indicating a clinically relevant role of cross-reactive T cells in chronic infections. Bei den hochgeladenen Daten handelt es sich um die Ergebnisse des Bulk-Sequenzierung des TCRbeta Repertoires von NP38- und NP205-spezifischen CD8 T-Zellen. Die Sequenzierung wurde an der MHH durchgeführt. Die Daten für die Sequenzierung wurden von Jasmin Mischke und Sebastian Klein aus der AG Cornberg/Kraft im Zeitraum März/April 2021 erhoben. Die Daten stehen als pdf Datei zur Verfügung.

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Mischke, J. / Klein, S. / Prinz, I. / et al: Protective cross-reactive T cell response in chronic lymphocytic choromeningitis virus infection upon Pichinde virus challenge. 2022. Medizinische Hochschule Hannover.

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