Immune deviation of 2C transgenic intraepithelial lymphocytes in antigen-bearing hosts

Sarah R. Guehler, Jeffrey A. Bluestone, Terrence A. Barrett

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


The present study examined self-tolerance for T cell receptor (TCR)αβ intestinal intraepithelial lymphocytes (iIELs) using the 2C transgenic (Tg) mouse model specific for a peptide antigen (Ag) presented by the class I major histocompatibility complex H-2L(d). Although Tg+ T cells were largely deleted from the periphery of Ag+ mice, equivalent numbers of Tg iIELs were present in Ag+ compared to Ag- mice. Tg iIELs in Ag- mice contained CD8αβ, CD8αα, and CD4+CD8+ subsets, whereas only CD8αα and CD4- CD8- Tg iIEL subsets were detected in Ag+ mice. Analysis of surface markers revealed that Tg iIELs in Ag+ mice expressed decreased levels of Thy-1 and increased CD45R/B220 as compared to Ag- Tg iIELs. In response to activation with exogenous peptide or immobilized anti-TCR mAb, iIELs from Ag- mice proliferated at high levels and produced interleukin (IL)-2 and interferon (IFN)-γ, while Tg+ iIELs from Ag+ mice proliferated at low levels and failed to produce detectable IL-2 or IFN-γ. Activation of sorted iIEL subsets from Ag mice revealed that CD8αα and CD4-CD8- subsets produced low levels of IL-2 and IFN-γ in response to activation with antigen- presenting cells and added peptide or immobilized anti-TCR mAb, while CD8αβ+ iIELs responded to endogenous levels of peptide. In response to APC and exogenous peptide, sorted iIEL subsets from Ag+ mice produced IL-2 and IFN-γ, and proliferated at greatly reduced levels compared to corresponding subsets from Ag mice. Analysis of cytokine mRNA levels revealed that activation in vitro induced IL-2 mRNA only in Ag-, but not Ag+ iIELs, whereas a high level of IL-4 mRNA reduction was detected in Tg+ iIELs from Ag+ mice, and to a lesser degree, from Ag- mice. These data suggest that tolerance for Tg+ iIELs resulted in the deletion of CD8αβ+ subsets and the persistence of Tg+ iIEL subsets with decreased sensitivity to endogenous levels of self-peptide. A comparison of the cytokine profiles expressed by Tg+ iIEL subsets in Ag- and Ag+ mice suggested that tolerance induction had involved the functional deviation of cells from TC1 (T helper-1-like) to a less inflammatory TC2 (T helper-2-like) phenotype capable of mediating humoral immune responses in the mucosa.

Original languageEnglish
Pages (from-to)493-503
Number of pages11
JournalJournal of Experimental Medicine
Issue number2
StatePublished - Aug 1 1996

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


Dive into the research topics of 'Immune deviation of 2C transgenic intraepithelial lymphocytes in antigen-bearing hosts'. Together they form a unique fingerprint.

Cite this