Migration and homing of lymphocytes to lymphoid and synovial tissues in proteoglycan–induced murine arthritis

Abstract

Objective. To describe the migration and homing of labeled donor lymphocytes to the lymphoid organs and synovial tissues of host animals, during the development of cartilage proteoglycan (PG)—induced arthritis adoptively transferred to syngeneic BALB/c mice. Methods. Lymphocytes from either nonarthritic or arthritic donor animals were labeled with either fluorescent or radioactive cell linkers (PKH–GL) and injected into syngeneic, immunosuppressed mice. The homing patterns of donor lymphocytes following the injection of labeled cells were studied by fluorescence microscopy and by measurement of radioactivity in tissue samples. Results. Lymphocytes from arthritic donors retained their ability to transfer the disease after labeling. In the lymphoid organs, arthritic and nonarthritic donor lymphocytes exhibited similar homing patterns, although remarkable differences were found in the number of homing cells derived from nonarthritic and arthritic donors. However, labeled cells only from arthritic animals migrated to the synovial tissue of the recipient mice, and their appearance was associated with the onset of arthritis. Conclusion. Lymphocytes from mice with PG–induced arthritis, in contrast to lymphocytes from nonarthritic donors, exhibit preferential homing to the synovial tissue of the host. Adoptive transfer of arthritis is linked to the appearance of these cells in the synovium.

Increased resistance to collagen-induced arthritis in CD44-deficient DBA/1 mice

“…Immunofluorescence staining of cell surface molecules, cell membrane labeling with PKH linkers (see below), and flow cytometric measurements were performed as described previously (16,31,37). In the case of adhesion receptors (e.g., L-selectin), the geometric mean of the fluorescence intensity was used to calculate the relative densities of these molecules on the surface of CD44 Ϫ/Ϫ and CD44 ϩ/ϩ cells.…”

“…Cells from wild-type donors were labeled with a green fluorescent cell linker (PKH67), and cells from CD44-deficient donors were labeled with a red fluorescent cell linker (PKH26). The fluorophores in these linkers are attached to a nontoxic lipophilic compound that does not interfere with cellular functions (37). CD44 ϩ/ϩ (green) and CD44 Ϫ/Ϫ (red) cells were suspended in phosphate buffered saline, mixed to achieve a 1:1 ratio (determined by 2-color flow cytometry), and 100 l of this suspension (containing 10 8 labeled cells) was injected intravenously into each recipient (7,37).…”

T and B Cell Recovery in Arthritis Adoptively Transferred to SCID Mice: Antigen-Specific Activation Is Required for Restoration of Autopathogenic CD4+ Th1 Cells in a Syngeneic System

“…Although the critical function of CD4 ϩ T cells was implicated in arthritis induction (16), the role of Abs to mouse (self) PG (mPG) and/or B cells in the pathogenesis of this autoimmune model is not yet fully understood (5,6,13). Transfer of the disease required both T and B cells, and neither anti-PG Abs nor PG-specific B cells alone were able to transfer disease (13,17). In contrast, PG-specific B cells appeared to play a major role in Ag presentation (5).…”

“…The disease can be transferred by coinjection of B and T cells into irradiated syngeneic mice (13,17). However, the incidence and severity of the disease are lower than in the donor BALB/c mice and the individual differences are relatively high among the recipients.…”

Cartilage proteoglycan-specific T cells as vectors of immunomodulatory biologicals in chronic proteoglycan-induced arthritis

“…In this study we examined the possibility to target inflammation in PGIA with ex vivo modulated PG-specific CD4 + T cells. Because arthritogenic and PG-specific T cells can migrate not only to the lymphoid organs but also to inflamed joints (Mikecz and Glant, 1994), they may be suitable tools to deliver such anti-inflammatory agents at the site of inflammation. Application of (genetically) modified CD4 + T cells expressing anti-inflammatory agents to successfully target autoimmune mediated inflammation was proposed and carried out previously .…”