FUNCTIONAL-DIFFERENTIATION OF T-CELLS IN THE INTESTINE OF T-CELL RECEPTOR TRANSGENIC MICE

The intestinal lamina propria (LP) is a major effector site of the muc osal immune system where antigen-specific and antigen-nonspecific fact ors shape the functional responses of CD4(+) T helper cells. To study the functional differentiation of LP T helper cells we utilized DO11.1 0 T cell receptor (TCR) transgenic (Tg) mice that expressed a clonotyp ic TCR specific for a class II major histocompatibility complex-restri cted peptide of chicken ovalbumin. The majority of cells expressing Tg TCR (Tg(+)) in peripheral lymphoid tissue expressed naive surface phe notypes whereas nearly all Tg(+) T cells in the intestinal LP expresse d an activated/memory-like phenotype. Flow cytometric analysis of Tg() T cell populations revealed that a small proportion of cells in peri pheral lymphoid tissue but nearly all cells in the LP expressed dual ( Tg plus non-Tg) TCRs. In Tg x recombinase-activating-gene-1-deficient (Tg x RAG-1(-/-)) mice, splenic and LP T cells expressed naive surface phenotypes and produced cytokines equivalent to naive splenic cells f rom Tg x RAG-1(+/+) mice. In contrast, Tg LP cells from Tg x RAG-1(+/) mice produced 35-fold greater levels of interferon-gamma and 5-fold greater levels of interleukin 4 compared with naive splenic cells. The se findings suggested that activation of Tg(+) T cells through endogen ous non-Tg TCR had promoted the localization and differentiation of me mory-like effector T helper cells in the intestine.