Immune deviation of 2C TCRαβ iels in AG-bearing hosts

We have utilized the 2C transgenic (Tg) mouse model specific for class I MHC H-2L^d alloantigen (Ag) to investigate self-tolerance for TCRaβ intestinal lELs. Compared to Tg T cell yields from syngeneic (Ag-) mice, fewer numbers of peripheral LN Tg T cells but equivalent numbers of Tg lELs were present in Ag+ mice. Tg lELs in Ag- mice contained CD8aβ, CDSaa, and CDS- subsets whereas only CDSact and COS- Tg IEL subsets were detected in Ag+ mice. Analysis of surface markers revealed that Tg lELs in Ag+ mice expressed decreased levels of Thy-1 and increased CD45R/B220 as compared to Ag- Tg lELs. Peripheral Tg T cells (CD8-) in Ag+ mice produced decreased levels of IL-2 but normal levels of IFN-y compared to Tg T cells (CDtaβ) in Ag- mice as measured by ELISA. However, compared to lELs from Ag- mice, Tg lELs from Ag+ mice proliferated less and produced reduced levels of IL-2 and IFN-y in response to APC + peptide or immobilized anti-TCR mAb. Assessment of cytokine mRNA production demonstrated that activation of Tg+ lELs from Agmice induced IL-2 but not IL-4 mRNA, whereas Tg+ lELs from Ag+ mice produced a reciprocal pattern with induction of IL4 but not IL-2 mRNA by activation to immobilized anti-TCR mAb in vitro. Thus, tolerance for Tg-dELs involved deletion of the CDSctβ subset along with functional differentiation of CDSoa and CD8subsets to a TC2-like phenotype. We speculate that immune deviation of I EL subsets may be a mechanism for directing potentially self-reactive T cells to less aggressive phenotypes.