THE ADOPTIVE TRANSFER OF CARTILAGE PROTEOGLYCAN (AGGRECAN)-INDUCED ARTHRITIS TO SCID MICE REQUIRES CO-ADMINISTRATION OF T CELLS AND ANTIGEN

8cells) or Lympholyte-purified spleen lymphocytes (2x10 7 cells, both T and B cells) injected together with PG (100�g intraperitoneally). SCID mice injected with splenocytes exhibited earlier arthritis (24±6.4 days after the injection) with lower severity (3.9±1.8 cumulative arthritis score), than those injected with purified lymphocytes (30±10.3 days onset and 7.7±1.9 severity score) (Fig.1). All these celltransfers from arthritic BALB/c mice into SCID mice resulted in 100% incidence, and the histopathology of the transferred disease was indistinguishable from those described in donor BALB/c mice. In contrast with the positive transfer system (described above), neither spleen cells nor lymphocytes without PG antigen were able to transfer the disease, also due to the lack of immune response PG antigen alone did not induce arthritis in SCID mice. While the non-specific lymphocyte stimulation (Concanavalin Afor T cells, LPS- for B cells) revealed no differences between the groups, the in vitro stimulation with PG was positive only in arthritic (lymphocyte plus PG-injected) SCID mice (Fig. 2.). The human PG co-injected arthritic SCID mice possessed a 600-fold higher antibody titer when compared with the SCID mice injected only with cells. This antibody titer in arthritic SCID mice was even higher than the titer measured in the donor arthritic BALB/c mice (Fig. 3.). Discussion/Conclusion This is the first report of an adoptive transfer of (PG-induced) arthritis into SCID mice. We observed 100 % incidence of arthritis in the SCID mice administered with immunologically active cells and the specific antigen (aggrecan) at the same time. SCID mice injected only with antigen-specific lymphocytes, however, could not develop arthritis. The clinical and histological appearance of arthritis in SCID mice was indistinguishable from the PG-induced arthritis in the donor BALB/c mice. This in vivo responsiveness and incidence of arthritis closely correlated with in vitro tests: T- and B-lymphocytes from cell plus antigen-injected SCID mice exhibited a high proliferation, antibody production and IL-2 secretion, whereas lymphocytes from SCID mice injected without PG antigen co-administration did not respond to in vitro stimulation. This observation clearly suggests that the presence of accessible antigen is pivotal in the maintenance of arthritis, whereas the antigen processing and the presentation of arthritogenic epitopes are intact in SCID mice. Our finding provides a very useful method to further investigate the mechanism of the development of arthritis and offers a special condition for studying cell-cell interaction, lymphocyte responses in vivo and in vitro conditions and the function of various lymphocyte subsets in any form of experimental arthritis.