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 mucosal immune system where antigen-specific and antigen-nonspecific factors shape the functional responses of CD4(+) T helper cells. To study the functional differentiation of LP T helper cells we utilized DO11.10 T cell receptor (TCR) transgenic (Tg) mice that expressed a clonotypic TCR specific for a class II major histocompatibility complex-restricted peptide of chicken ovalbumin. The majority of cells expressing Tg TCR (Tg(+)) in peripheral lymphoid tissue expressed naive surface phenotypes whereas nearly all Tg(+) T cells in the intestinal LP expressed an activated/memory-like phenotype. Flow cytometric analysis of Tg(+) T cell populations revealed that a small proportion of cells in peripheral lymphoid tissue but nearly all cells in the LP expressed dual (Tg plus non-Tg) TCRs. In Tg × recombinase-activating-gene-1-deficient (Tg × RAG-1(−/−)) mice, splenic and LP T cells expressed naive surface phenotypes and produced cytokines equivalent to naive splenic cells from Tg × RAG-1(+/+) mice. In contrast, Tg LP cells from Tg × RAG-1(+/+) mice produced 35-fold greater levels of interferon-γ and 5-fold greater levels of interleukin 4 compared with naive splenic cells. These findings suggested that activation of Tg(+) T cells through endogenous non-Tg TCR had promoted the localization and differentiation of memory-like effector T helper cells in the intestine.