3.3.1: T cells and DN T cells in SLE.
As discussed in the introduction, the pathogenesis of SLE has been established as a T cell dependent process prompting a detailed study of the numbers and functions of this group of cells, in patients with SLE (Cohen, 1993). In this study, we did not find increased
percentages of T cells in patients with SLE, compared to RA patients and healthy controls. An increased percentage of CD3^T cells, in patients with SLE, was reported by Erkeller-Yüksel et al, in 1993 (Erkeller-Yusel et a l, 1993). In contrast, other studies have found a decrease in T cell percentages in SLE patients when compared to healthy controls (Glinski et a l, 1976; Smolen et a l, 1982). We examined the percentages of CD3^ T cells in patients with SLE and found them unchanged, when compared to both autoimmune disease controls (RA patients) and healthy individuals. The variable results reported in the numbers of T cells in SLE patients might be because of the larger cohort of patients (71 patients) in some of the studies (Erkeller-Yusel et a l, 1993) and the heterogeneous nature of patients included in each of the studies.
I also failed to find an increase in the total DN T cell population (ap or yô TCR expressing DN T cells) in SLE patients we studied compared with autoimmune controls (RA patients) and healthy subjects. This is in contrast to some previous reports on the total DN T cell population in SLE. These studies have indicated the presence of increased percentages of this population in patients with SLE (Lacki et a l, 1997; Devi et a l, 1998). These reports also indicated that in patients with SLE who have consistently elevated levels of DN T cells, treatment with corticosteroids and cyclophosphamide reduced the percentages of these cells. Interestingly, although my data does not suggest a statistically significant expansion in the total DN T cell population in SLE patients compared to RA patients and healthy controls, a few patients in the study showed a large increase in their DN T cell population though this was not related to their disease activity. We studied this population in patients with variable
disease activity (as indicated by their disease activity global score) and could find no correlation between the percentages of total DN T cells and disease activity. The patient population studied, consisted of both patients receiving immunosuppressive therapy and those receiving no drug treatment.
3.3.2: a P TCR^ D N T cells in SLE.
On further analysis of the DN T cell populations expressing either the aP or yô TCRs, the percentages of a p TCR^ DN T cells in patients with SLE, within the total DN population were significantly increased compared with RA and HC. It is unlikely that the observed increase was a result of therapy because, although many of the patients were receiving
steroids, either alone or in combination with other drugs, eight patients were not receiving any major drugs. There was no significant increase in the numbers of a p TCR^ DN T cells in patients with RA compared with HC demonstrating that this expanded population is specific to SLE. These data are consistant with other reports of expanded populations of aP TCR^ DN T cells in patients with autoimmune diseases such as SLE and systemic sclerosis (Shivakumar et al., 1989; Sakamoto et a i, 1992; Liu et al., 1998; Sieling et al., 2000). On the other hand, long term clonal proliferation of a p TCR^ DN T cells was not found to be associated with any history of severe illness in two apparently healthy subjects (Kusunoki et al., 1992).
3.3.3: CD3:TCR complex on a p TCR-\-ve DN T cells.
One of the distinctive characteristics of aP TCR^ DN T cells previously reported, is the expression of lower levels of the CD3: TCR complex on the cell surface. My data show that the density of expression of both CD3 and the a p TCR (as indicated by the MFI of anti- CD3 or TCR a p surface staining) was found to be reduced significantly in SLE DN T cells, when compared to CD4^ or CD8^T cells. Interestingly this decreased expression of CD3 was not peculiar to SLE since it was found in patients with RA, healthy individuals and has been previously reported in, patients with adult T cell leukemia (ATL), systemic sclerosis and in murine DN T cells (Murison et a l, 1993; Sakamoto et a l, 1992; Suzushima et a l, 1993; Huang and Crispe, 1992). My data also suggests a significant reduction in CD3 expression on all aP TCR^ DN T cells compared with yô TCR^ DN T cells. This characteristic was also common to DN T cells from patients with SLE, RA and healthy individuals. Surprisingly, the CD3: TCR complex has been shown to be functionally competent in a p TCR^ DN T cells, so the functional significance of the paucity of CD3: TCR expression is unclear and requires further study (Groh et a l, 1989; Rivas et a l, 1990; Matsumoto et a l, 1991).
3.3.4: y ô T cells in SLE.
No change in the percentage of total TCR yô expressing T cells (both DN and CD8^) in patients with SLE compared to RA or HC was seen in this study. This observation, however does not rule out a role for this population as the yô T cells in the particular patients included in our study might have been ‘trafficked away’ to the sites of local inflammation in various organ systems. The role of yô T cells in patients with SLE is the subject of many contradicting reports in literature. Although some investigators suggest an expansion of this population in the peripheral blood of patients with SLE, others report unchanged or decreased numbers in the peripheral blood (Gerli et a l, 1991;Riccieri et al., 2000 ; Robak et al., 2001 ; Robak et a l,
1999).