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

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 CD8⁺ T 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: T_H1, T_H2, T_H17, and regulatory T cells (Tregs). In swine, knowledge about these functionally characterized subsets is still rudimental and a range of open questions exists. T_regs, 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 T_H1, T_H2 and T_H17 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 T_H17 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 T_H1 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.