Pathogenic role of T cells in
outnumber the beneficial effects, a great deal of effort has focused on selectively targeting autoimmune diabetes only those T cells involved in the disease process. 17 For aiming and selecting disease-associa-Insulin-dependent diabetes mellitus (IDDM) ted autoreactive T cells it is important to detect, results from cell-mediated autoimmune attack define and characterize them as appropriate directed towards the insulin-producing islets of target cells. Islet antigen-reactive T cells are Langerhans, which leads to specific destruction detectable not only in IDDM patients but also of the pancreatic β€-cells. The central role of T in healthy control subjects, although they cells in the pathogenesis of autoimmune diaappear less frequently and less reactive in the betes has been demonstrated in several ways. latter group. Even though it is well known that In the NOD mouse, which spontaneously self-reactive T cells that have escaped thymic develops diabetes similar to human IDDM, β€selection are not exceptional, 18 it remains to be cell destruction is prevented by neonatal thyestablished how self-tolerance or ignorance in mectomy 1 as well as antibody treatment aiming the periphery is maintained in healthy subjects T cell subsets expressing the surface markers whereas the control mechanisms fail regulating CD3, CD4 or CD8. [2][3][4][5] Insulitis and diabetes can autoreactive T cells in patients developing autobe adoptively transferred with T lymphocytes immune disease. T cell responses in the periphfrom diabetic mice into non-diabetic recipiery are determined by several intrinsic mechents. [6][7][8][9][10] In humans, immunosuppressive theranisms, such as T cell maturation in the apy delays diabetes onset similar to the mouse thymus, location and nature of the antigen and situation, 11,12 T cells reactive to IDDM-associalevel and timing of antigen expression. 19,20 The ted autoantigens are detectable in diabetic subinheritance of certain genetic alleles and jects, 13 insulitis recurs after transplantation of exposure to pathogens can contribute to the pancreatic grafts in IDDM patients 14,15 and failure or success in keeping these autoreactive IDDM can incidentally be transferred by trans-T cells under control. 18 Further detailed characplantation of bone marrow of a diabetic patient terization of islet autoantigen-specific T cells in to an immunodepressed non-diabetic recipianimal models and in human IDDM subjects is ent. 16 warranted to unravel their role in autoimmune Since the negative side-effects of unspecific destruction. T cell clones are especially suited immunosuppressive therapy in human IDDM for these kinds of investigations, since they consist of a homogeneous and stable cell population which is derived from one single precur-