Differential antigenic stimulation influences cytokine production patterns in T cells and CD4+ subpopulations

The regulatory mechanisms that govern the commitment of T cells to a Th1 or Th2 lineage in terms of cytokine production patterns have not yet been fully elucidated. The authors have endeavored to study the role of the antigen in regulating the production of cytokines. To study this matter, a panel of antigens was chosen to include two random poly amino acids, PA1 (Poly(1-Phe, L-Glu)Poly-dL-Ala-PolyL-Lys), PA2 (Poly(Glu-NaAla), and two purified protein derivatives PPD1 (H37Rv virulent) and PPD2 (H37Ra non-virulent) obtained from WHO strains of Mycobacterium tuberculosis. After in vivo priming, murine spleen cells were prepared and three groups of cells (unfractionated, T cells, and CD4+ populations) were each separately stimulated in vitro with the original antigen Staphylococcal enterotoxin B (SEB) and phorbol myristate acetate (PMA). ELISA assays were subsequently performed on supernatants for IL-4, IL-5, IL-2 and IFN-g. The results indicate a different cytokine pattern for the various antigenic stimulations. The PPD1 induced IL-5 production, while the PPD2 induced high levels of IFN-gamma. SEB was shown to exert a strong effect on the cytokine profile shifting it towards a Th1-like profile. A comparison is made between the cytokine patterns in different cells. The role of antigens and superantigens in regulating cytokine production and determining the outcome of the pathological process in relation to other regulatory factors is discussed.