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 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 from 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. 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.
Hurst
S D
SD
Department of Medicine, Lakeside Veteran's Administration Hospital and Northwestern University Medical School, Chicago, IL 60611, USA.
Sitterding
S M
SM
Ji
S
S
Barrett
T A
TA
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D018014:Gene Transfer Techniques; D007422:Intestines / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D011948:Receptors, Antigen, T-Cell