<<Disclaimer: Verify this information before applying it to your situation.>>

I just wanted to comment on the following articles which were just cited on
PubMed.  In these articles, it is found that there appears to be an absence
of "double positive" CD4CD8 T cells in celiacs, on both GF and non-GF
diets.  Coincidentally I have been in the process of preparing a near-
future posting about tin as an essential trace element on this List which,
in part, briefly discusses the function of the thymus gland.  It just so
happens that the thymus gland is a central and primary site where large
numbers of these "double positive" CD4CD8 T cells are generated.  The
thymus gland is particularly sensitive to malnutrition and to essential
trace element deficiencies, especially zinc.  Since celiac disease is a
malabsorption disease, one would expect the thymus gland and its T cell
production to be very much affected by celiac disease.  I believe the
article's finding of depleted "double positive" CD4CD8 T cells in celiacs
is a result of malabsorption and mineral deficiences rather than some
inherent part of the pathogenesis of celiac disease.  However, these
articles can be taken as evidence that the thymus gland is indeed affected
by celiac disease.  I'll have more about the thymus gland in my future
posting on tin.

----------
Eur J Gastroenterol Hepatol. 2004 Oct;16(10):957-8.

Intra-epithelial T cells in coeliac disease.

Watson RG, Johnston SD.

Dept of Medicine, Institute of Clinical Science, Royal Victoria Hospital,
Belfast; and Dept of Gastroenterology, Belfast City Hospital, Belfast, UK.

In coeliac disease dietary gliadin is damaging to the small intestinal
mucosa.It occurs in individuals with a genetic predisposition.In terms of
pathogenesis the link between genetics and the toxic effects of gliadin
remains obscure.  A study in this issue of the Journal demonstrates an
inherent absence of double positive CD4CD8 T cells in coeliac patients. It
is suggested that this could result in a loss of oral tolerance and play a
role in the mucosal damage of coeliac disease.  In addition, it is
confirmed that intra-epithelial lymphocytes are not increased in coeliac
disease but there is an apparent increase due to the change in
architecture, and decrease in enterocytes.  Coeliac disease is an
enteropathy associated with dietary gluten which occurs in individuals with
a genetic predisposition. The pathogenesis remains obscure although it is
clear that only certain parts of the gliadin molecule are toxic and there
is considerable evidence of immunological activity, including antibody
production. In this issue of European Journal of Gastroenterology and
Hepatology Carton et al. present evidence in favour of an inherent
depletion of CD4CD8 T cells, which could result in a loss of oral tolerance
to ingested gliadin. Using flow cytometry they also demonstrated that the
classic T-cell infiltration of coeliac disease is not due to an increase in
T cells but is an apparent increase associated with a relative decrease in
enterocytes as a result of the change in architecture of the mucosa. These
could be important fundamental observations in helping to unravel the
pathogenesis of coeliac disease.

PMID: 15371916 [PubMed - in process]

----------
Eur J Gastroenterol Hepatol. 2004 Oct;16(10):961-8.

CD4+CD8+ human small intestinal T cells are decreased in coeliac patients,
with CD8 expression downregulated on intra-epithelial T cells in the active
disease.

Carton J, Byrne B, Madrigal-Estebas L, O'Donoghue DP, O'Farrelly C.

Education and Research Centre and Dept of Gastroenterology, St Vincent's
University Hospital, Dublin; Institute of Immunology, National University
of Ireland Maynooth, Co. Kildare; and Conway Institute, University College
Dublin, Ireland.

BACKGROUND/OBJECTIVE: The intestinal lesion of coeliac disease is thought
to be initiated and exacerbated by dysregulation of local T-lymphocyte sub-
populations. This study examines changes in intestinal T cells from coeliac
patients, with a particular focus on CD4CD8 T cells, immunoregulatory cells
normally found in relatively high proportions in the small intestine.
METHODS: Cells were obtained from duodenal biopsies from active and treated
coeliac patients using chelating and reducing agents (epithelial layer)
followed by collagenase treatment (lamina propria). Cell yield and
viability were assessed and flow cytometric analysis was used to examine
CD4CD8 T cells and to quantify CD8 expression. RESULTS: Surprisingly, total
T-cell yields in the epithelial layer did not increase in active coeliac
disease although enterocyte counts decreased significantly, giving an
appearance of infiltration. In active coeliac patients, CD4CD8 T cell
percentages were significantly decreased in both the epithelial layer and
lamina propria. Levels of CD8 expression by CD4CD8 T cells in the
epithelial layer were decreased significantly in patients with active
coeliac disease. CD4CD8 T cell proportions did not return to normal in
treated coeliac patients whose villous architecture had responded to gluten
withdrawal. CONCLUSIONS: No increase of intra-epithelial lymphocytes in the
coeliac lesion may require us to reconsider the definition of coeliac
disease as an inflammatory condition. Low CD4CD8 populations in treated as
well as untreated coeliac patients indicate that these T cells are
inherently absent in individuals genetically predisposed to coeliac disease.

PMID: 15371918 [PubMed - in process]

* * *

* Please remember some posters may be WHEAT-FREE, but not GLUTEN-FREE *