Normal T-helper 1/T-helper 2 balance in peripheral blood of coeliac disease patients.

Activated T cells, with their secretion of cytokines, probably play an important role in the pathogenesis of mucosal lesions in coeliac disease (COD) and the prominence of a T-helper (Th)1-type cytokine pattern has been reported. As the process of immunological activation in the jejunal mucosa in active CoD has been shown to also cause some differences in peripheral blood lymphocyte populations, we sought to establish any changes in the Th 1/Th2 balance in peripheral blood of patients, at different stages of CoD, relative to healthy individuals. Twenty-two CoD patients and 10 healthy controls were included in the study. The Th1/Th2 balance was examined both in resting cells and after polyclonal stimulation using two different methods: intracytoplasmic cytokine contents were measured using an intracellular staining method and three-colour flow cytometry and cytokine contents of cell culture supernatants were measured using traditional enzyme-linked immunosorbent assays (ELISAs). Interferon-gamma (IFN-gamma)-producing cells (Thl) were as prominent in untreated CoD patients and treated CoD patients as in healthy controls, while cells fitting a Th2 or ThO-type cytokine pattern were few in all groups. In ELISA assays, Th1 type (IFN-gamma or interleukin (IL)-2) cytokines were again prominent in all study groups but no statistically significant differences were found in IFN-gamma, IL-4 or IL-2 levels among the three groups. These results suggest that the increased shift towards a Th1 response is mainly restricted to the actual site of inflammation and that circulating T cells do not show a similar response, presumably because activated cells in peripheral blood are too few. Further research on cytokine profiles measuring T-cell activation in CoD should be focused on the actual tissue of inflammation.

Circulating T lymphocyte subsets in coeliac disease (CoD) patients and healthy family members.

Increased proportions of circulating antigen-primed CD45RO+ TCR gammadelta cells have been found in untreated CoD patients. As certain immunological features are now found in both CoD and healthy persons carrying the HLA DQ2 heterodimer, we sought to establish whether healthy members of the families of CoD patients who are positive for HLA DQ2 and also have increased densities of TCR gammadelta intraepithelial lymphocytes (IEL) in their small bowel mucosa have elevated levels of circulating TCR gammadelta memory cells. Peripheral blood T cells were analysed by flow cytometry in 22 patients with CoD and 16 healthy family members. Untreated CoD patients had higher percentages of circulating CD45RO+ TCR gammadelta cells and CD45RO+ Vdelta1+ cells than healthy family members. On the other hand, the amount of circulating Vdelta1+ lymphocytes was lower in patients with CoD compared with healthy family members. In contrast, no differences were found between HLA DQ2+ and HLA DQ2- healthy family members in respect of circulating TCR gammadelta cell subsets. The change in circulating TCR gammadelta cell subsets found in patients with CoD is thus a consequence of an ongoing immunological process which diminishes on a gluten-free diet rather than a phenomenon directly caused by DQ2. These changes in peripheral blood are not found in healthy individuals who have the same HLA alleles DQA1*0501 and DQB1*0201 encoding the HLA DQ2 and who also have increased densities of TCR gammadelta IEL in their otherwise normal jejunal mucosa.

Distinct immunologic features of Finnish Sjögren's syndrome patients with HLA alleles DRB1*0301, DQA1*0501, and DQB1*0201. Alterations in circulating T cell receptor gamma/delta subsets.

OBJECTIVE: To determine whether there were differences in the circulating T lymphocyte subsets or clinical features of patients with primary Sjögren's syndrome (SS) who were positive for different HLA alleles. METHODS: Two- and three-color flow cytometry analyses were performed, using a whole blood lysing method. RESULTS: Patients with SS who had the HLA alleles DRB1*0301, DQA1*0501, and DQB1*0201 had lower levels of circulating V delta 1-positive T cell receptor gamma/delta (TCR gamma/delta) cells and higher levels of circulating CD45RO-positive TCR gamma/delta cells compared with patients with SS who did not have these alleles. The patient subgroup with these alleles also had higher levels of anti-SS-A/Ro and anti-SS-B/La. CONCLUSION: These results indicate that patients with primary SS may be immunologically divided into subgroups according to their HLA status. These immunologic changes in SS may also be typical of other autoimmune disorders in patients with the HLA-DR3 haplotype.

Phenotypical characterization of peripheral blood T cells in patients with coeliac disease: elevation of antigen-primed CD45RO+ T lymphocytes.

Increased numbers of gamma delta T-cell-receptor-bearing (TCR gamma delta +) lymphocytes are present in the small intestinal epithelium of patients with coeliac disease (CoD). In this study the phenotypic characteristics of peripheral blood T cells from 14 untreated CoD patients and 14 healthy age- and sex-matched controls were determined with special emphasis on TCR gamma delta + lymphocytes. We also studied samples taken from 15 CoD patients who were on gluten-free diet (GFD). Two- and three-colour flow cytometry analyses were performed using a whole-blood lysing method. There was no significant difference between the percentages of TCR gamma delta + lymphocytes in patients and controls. However, the amount of delta TCS1+ lymphocytes was significantly lowered in untreated patients (0.48 +/- 0.42% in CoD versus 0.86 +/- 0.57% in controls, P < 0.05). The percentage of CD45RO+ T cells, which are a primed population of T cells including memory cells, was significantly raised in the peripheral blood of untreated patients. This phenomenon was most prominent within the TCR gamma delta + population (83.9 +/- 12.2% in CoD versus 65.5 +/- 14.7% in controls, P < 0.01), but the same applies to CD45RO+ TCR alpha beta + and delta TCS1+ T cells. In patients on GFD these changes seem to be at least partly corrected. Antigen-primed CD45RO+ T cells have been shown to accumulate in the jejunal epithelium of patients with untreated CoD. The enhanced 'memory activity' also found in the peripheral blood of untreated CoD patients may result from a continuous antigenic stimulus and this stimulus could be gluten triggered.