Analysis of Leukocytes Recruited to the Pancreas by Diabetogenic T Cell Clones

Recruitment and Activation of Macrophages by Pathogenic CD4 T Cells in Type 1 Diabetes: Evidence for Involvement of CCR8 and CCL1

“…These studies and others have established that there are large numbers of F4/80 ϩ and CD11b ϩ macrophages in the pancreatic infiltrates of NOD mice, both in spontaneous disease and in adoptive transfers of diabetogenic T cells (2,3). The requirement for macrophages in the pathogenesis of type 1 diabetes (T1D) 3 has been shown in studies in which disease was inhibited by their depletion (4,5).…”

“…A doptive transfer of diabetogenic CD4 Th1 T cell clones into young NOD or NOD.scid recipients rapidly induces onset of diabetes and also provides a system for analysis of the cellular components of the pancreatic inflammatory infiltrate (1,2). These studies and others have established that there are large numbers of F4/80 ϩ and CD11b ϩ macrophages in the pancreatic infiltrates of NOD mice, both in spontaneous disease and in adoptive transfers of diabetogenic T cells (2,3).…”

A Metalloporphyrin-Based Superoxide Dismutase Mimic Inhibits Adoptive Transfer of Autoimmune Diabetes by a Diabetogenic T-Cell Clone

“…Harhaj and Sun (71) reported that free-radical generation and cytokine production by primed APCs are critical for early T-cell signaling events. Although the T-cell clone BDC-2.5 can normally be detected in the pancreas after adoptive transfer (72), APCs in the pancreas of SOD mimic-treated recipients may be unable to activate the clone to produce IFN-␥ and, consequently, the T-cells leave the pancreas and move to a secondary lymphoid organ such as the spleen. In fact, we detected BDC-2.5 in the spleen of SOD mimic-treated recipient NOD.scid mice after transfer (data not shown).…”

In situ recognition of autoantigen as an essential gatekeeper in autoimmune CD8+T cell inflammation

“…Studies in a number of infection and autoimmune disease models have suggested that recruitment of T lymphocytes into a site of extralymphoid inflammation does not require local expression of cognate (foreign or self) pMHC on tissue cells or tissue-associated antigen-presenting cells (APCs) (4-7). Accordingly, it is generally thought that non-antigen-specific inflammatory cues such as cytokines and chemokines emanating from the local microenvironment can recruit noncognate (i.e., bystander) T cells to a site of foreign or self antigen-triggered tissue inflammation (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). Notwithstanding that in vitro-activated bystander T cell clones can transiently comigrate with their cognate counterparts into noninflamed tissue in adoptive T cell transfer experiments and that tissue-specific expression of cytokine and/or chemokine transgenes in normal tissues can trigger bystander T cell inflammation, these models do not faithfully mimic the events that take place in spontaneous autoimmune inflammation.…”