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Porcine T lymphocytes and their contribution to an effective immune response after vaccination

Published: October 10, 2014
By: A Saalmüller1, S Talker1, H Koinig1,2, K Mair1, K Reutner1, C Sedlak1, IM Rodríguez-Gómez1, T Käser3, A Ladinig2,4, SE Essler1, M Patzl1, M Ritzmann5, I Hennig-Pauka2, W Gerner1 ( 1Institute of Immunology, Dept. of Pathobiology, University of Veterinary Medicine Vienna, Austria, 2University Clinic for Swine, Dept. for Farm Animals and Veterinary Public Health, University of Veterinary Medicine Vienna, Vienna, Austria,3VIDO-InterVac, University of Saskatchewan, Saskatoon, Canada, 4 Western College of Vete
T cells play a central role in the immune response after infection and vaccination. Two main groups of T cells can be discriminated: T cells with antigen-specific T-cell receptors (TcR) consisting of α and β chains which represent the “classical” T cells, and T cells with TcR γδ chains with less characterized immunological functions. In swine, TcR γδ T cells are a prominent and heterogeneous T-cell subpopulation that is characterized by IFN-γ and IL-17 production. CD2+γδ T cells are mainly responsible for IFN-γ production, whereas IL-17 producers belong in their majority to the CD2- subset. Beside these functions after polyclonal activation the specific ligands recognized by the respective γδ TcR and the corresponding antigen-specific activation are currently unknown.
Within the TcR αβ T cells two main subsets are characterized: major histocompatibility class I (MHC-I) restricted CD8T cells with mainly cytolytic effector functions and MHC-II restricted CD4+ T cells. These CD4+ T cells are involved in the fine tuning of immune responses of the innate as well as the adaptive immune system. After activation via MHC-II presented peptides, CD4+ T cells differentiate into various effector cell populations to accomplish their diverse functions. As a consequence, the differentiated CD4+ population represents a functionally heterogeneous population containing a panel of cell subsets with different effector functions: TH1, TH2, TH17, and regulatory T cells (Tregs). In swine, knowledge about these functionally characterized subsets is still rudimental and a range of open questions exists. Tregs, identified by the expression of the transcription factor Foxp3, play a crucial role in the down-regulation and modulation of immune responses and in swine the majority of them are defined by a co-expression of CD4 and CD25. Especially CD4+ T cells with high CD25 expression show cell-cell contact dependent regulatory activity. CD25 low positive CD4+ cells seem to be potent producers of IL-10. For an efficacious vaccination these cells might have a negative impact and a stimulation of this subset has to be avoided. More important for a protective immune response are TH1, TH2 and TH17 cells. In contrast to the naïve CD4+ T-cell subpopulation, porcine differentiated CD4+ T cells show the peculiarity of a CD8α expression. The CD4+CD8α+ T cell subpopulation contains activated as well as memory Thelper cells. CD4+CD8α+ T cells showing a production of IL-17 can be characterized as porcine TH17 cells with the capacity for stimulation of neutrophils and are therefore involved in the immune response against bacterial antigens.

IFN-γ and TNF-α producing T cells are also included in the heterogeneous CD4+CD8α+ subpopulation and represent porcine TH1 cells. CD27 expression discriminates CD4+CD8α + T cells into CD27+ and CD27- cells with characteristics of central and effector memory T-helper cells, respectively.
The generation of CD4+ memory T cells is a hallmark of efficacious vaccines. Consequently, these vaccine antigenspecific memory T cells should be detectable in functional assays. ELISpot analyses can be used to detect the frequency of vaccine-antigen specific IFN-γ, TNF-α or IL-17 producing cells and thereby enable a quantitative analysis of memory cells induced by vaccination. More detailed analyses can be performed by flow cytometry (FCM). FCM enables the identification of the phenotype of antigen-specific cytokine producing cells. Thereby, the involvement of CD8+ cytolytic T cells or the detailed phenotype of the CD4+ T cell population in regard to central or effector memory cells can be identified. Furthermore, FCM provides the possibility to detect multi-functional T cells producing two and more cytokines on the single cell level. The presence of multi-functional T cells may represent a correlate of a successful immune-stimulation. Whether these T cells will furthermore represent correlates of protection has to be elucidated for each vaccine and for each infectious disease.
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Authors:
Armin Saalmueller
University of Veterinary Medicine Vienna
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