Subsets of CD3<sup>+</sup> (T cell receptor α/β or γ/δ) and CD3<sup>−</sup> lymphocytes isolated from normal human gut epithelium display phenotypical features different from their counterparts in peripheral blood

Encephalitozoon cuniculi continues to pose a problem for immunocompromised patients. Previous studies from our laboratory have elucidated the importance of the CD8+ T cell subset in the protection against systemic parasite infection. There have been no studies related to the mucosal immunity induced against this orally acquired pathogen. In the present study, the immune response generated in the gut after oral E. cuniculi infection was evaluated. An early and rapid increase of the intraepithelial lymphocyte (IEL) population of orally infected animals was observed. This increase in the IEL population started as early as day 3 and peaked at day 7 postinfection with persistent elevation thereafter. At day 7 postinfection, IELs expressed strong cytokine messages (IFN-γ and IL-10) and were highly cytotoxic for parasite-infected syngeneic macrophages. At an E:T ratio of 80:1, these cells were able to cause >60% Ag-specific target cell lysis. A significant increase in the CD8αα subset of IEL in response to an oral E. cuniculi infection was observed. To the best of our knowledge, such an early expansion of an IEL population exhibiting strong ex vivo cytotoxicity has not been reported with infectious models. These data suggest that IELs act as important barriers for multiplication of this organism leading to the successful resolution of infection. The protective role of IELs may be due both to their inflammatory (IFN-γ production and cytotoxic response) as well as immunoregulatory (IL-10 production) properties.

Section: Discussionmentioning

confidence: 99%

Induction of a Rapid and Strong Antigen-Specific Intraepithelial Lymphocyte Response during Oral Encephalitozoon cuniculi Infection

Moretto

Weiss

Khan

2004

“…Ϫ 7 ϩ population is present in the gut epithelium that expresses NK markers (18,23,24), and a subset displays intracellular CD3⑀ found in NK and T progenitor cells (25,26). We first investigated LPLs isolated from four human fetal gut samples of 12.8 -13.3 wk gestation for their NK marker expression by flow cytometric analysis.…”

Section: Human Fetal Cd3 ϫ 7 ϩ Lpls Express a Distinct Pattern Of Nk mentioning

confidence: 99%

Phenotypic Characterization of CD3−7+ Cells in Developing Human Intestine and an Analysis of Their Ability to Differentiate into T Cells

Günther

Holloway

Gordon

et al. 2005

We have identified a large population of CD3−7+ cells in human fetal gut. Three- and four-color flow cytometry revealed a distinct surface Ag profile on this population; the majority were negative for CD4 and CD8, whereas most of the remainder expressed the CD8αα homodimer. In contrast about half of CD3+ cells expressed CD4 and half expressed CD8α. A large proportion of CD3−7+ cells expressed CD56, CD94, and CD161, and whereas CD3+ T cells also expressed CD161, they only rarely expressed CD56 or CD94. Further studies were conducted to determine whether the CD3−7+ cells have the potential to differentiate into CD3+ cells. About half of CD3−7+ cells contain intracellular CD3ε. Rearranged TCR γ-chains were detected in highly purified CD3−7+ cells as an early molecular sign of T cell commitment, and the pattern of rearrangement with V regions spliced to the most 5′ Jγ segment is reminiscent of early thymocyte differentiation. In reaggregate thymic organ cultures, CD3−7+ cells also gave rise to CD3+ T cells. Thus, we demonstrate that the CD3−7+ cells present in the human fetal gut display a distinct phenotype and are able to develop into CD3+ T cells.

“…The close linkage and coexpression of the CD8 genes suggest coordinate regulation. However, regulation is not always coordinated, particularly in cells which seem to be extrathymically derived, as subsets of human NK cells (4) and gut intraepithethelial lymphocytes (IELs) 3 (5,6) express only the CD8␣␣ homodimer. Toward identifying cis-acting transcriptional regulatory elements in the CD8 loci, large fragments of genomic DNA have been used to make transgenic mice.…”

Section: Cd8 Gene Complex By Colocalization Of Dnase I Hypersensitivementioning

confidence: 99%

Identification of a Candidate Regulatory Region in the HumanCD8Gene Complex by Colocalization of DNase I Hypersensitive Sites and Matrix Attachment Regions Which Bind SATB1 and GATA-3

Kieffer

Greally

Landres³

et al. 2002

To locate elements regulating the human CD8 gene complex, we mapped nuclear matrix attachment regions (MARs) and DNase I hypersensitive (HS) sites over a 100-kb region that included the CD8B gene, the intergenic region, and the CD8A gene. MARs facilitate long-range chromatin remodeling required for enhancer activity and have been found closely linked to several lymphoid enhancers. Within the human CD8 gene complex, we identified six DNase HS clusters, four strong MARs, and several weaker MARs. Three of the strong MARs were closely linked to two tissue-specific DNase HS clusters (III and IV) at the 3′ end of the CD8B gene. To further establish the importance of this region, we obtained 19 kb of sequence and screened for potential binding sites for the MAR-binding protein, SATB1, and for GATA-3, both of which are critical for T cell development. By gel shift analysis we identified two strong SATB1 binding sites, located 4.5 kb apart, in strong MARs. We also detected strong GATA-3 binding to an oligonucleotide containing two GATA-3 motifs located at an HS site in cluster IV. This clustering of DNase HS sites and MARs capable of binding SATB1 and GATA-3 at the 3′ end of the CD8B gene suggests that this region is an epigenetic regulator of CD8 expression.