Th1-, Th2- & Th17-Type Cytokine Profiles in CD4-dnTGFβRII Mice

Objectives: CD4-dominant negative TGFβRII (TbRII) transgenic mice develop an autoimmune phenotype characterized by mononuclear cell infiltration into multiple organs and spontaneous activation and differentiation of T cells in lymphoid tissues. The systemic cytokine profile of naïve TbRII mice is dominated by IFN-γ production by CD8⁺ T cells, as well as Th1- and Th2-type cytokine production. In this study, we used intracellular cytokine staining to determine the precise mucosal cytokine profile of these mice.

Methods: Mononuclear cells from various lymphoid tissues were isolated from naïve mice or mice given oral OVA (1 mg) plus native cholera toxin (nCT; 15 μg). Cells were stained intracellularly with fluorescence-conjugated cytokine-specific monoclonal antibodies (mAbs), and were subjected to FACS analysis.

Results: There were no significant increases in Th1-, Th2- or Th17-type cytokine production in systemic and mucosal immune tissues of young adult TbRII mice. However, by six months of age, a marked increase in IFN-γ production by CD4⁺ T cells was seen in systemic and mucosal lymphoid tissues. The most significant increase in IFN-γ production was in the small intestinal lamina propria (iLP) where one half of all CD4⁺ T cells produced IFN-γ. Th2- and Th17-type cytokine production was relatively unchanged between young adult and aging mice. Upon oral immunization with OVA plus nCT as adjuvant, young adult TbRII mice showed a dramatic increase in CD4⁺ production of IL-17 in the iLP.

Conclusion: It has recently been shown that differentiation of T helper precursor cells into Th17 cells relies on TGF-β signaling, for this reason we are currently confirming these data and are seeking an alternative pathway for IL-17 induction by CD4⁺ cells in mice given oral OVA plus nCT.

Supported by NIH grants AG 025873, DE 12242, AI 18958 and AI 43197 and a Graduate School Fellowship through the School of Dentistry, UAB.