Cell migration studies in the adoptive transfer of adjuvant arthritis in the Lewis rat.

Adjuvant arthritis (AA) can be induced in Lewis rats by a single injection of either heat-killed Mycobacterium tuberculosis or the lipoidal amine CP20961. Concanavalin A (Con A)-stimulated T cells isolated from AA rats are able to adoptively transfer the disease to naive syngeneic recipients. It is unclear, however, whether these transferred cells traffic directly to the joint and initiate arthritis, or whether secondary host cells are responsible for activation of the disease. In the current investigation, T cells labelled with the vital fluorescent dyes Hoechst H33342 and Zynaxis PKH26-G were used to adoptively transfer adjuvant disease to naive recipients. At various stages of disease development sections of ankle joints, together with a range of soft tissues, were examined by fluorescence microscopy to determine the distribution of labelled donor cells in the recipients. Intensely fluorescent lymphocytes were observed in the liver, spleen and lymph nodes within 24 hr of adoptive transfer. Foci of such cells were clearly visible in the primary lymphoid tissues as late as 14 days after transfer. However, close examination of both ankle joint sections and patellar fat pad cells throughout the time-course of the study failed to detect any labelled cells at the lesion site. To develop these observations further, we performed adoptive transfers to nude Lewis rats (rnu/rnu) and found that they were only moderately sensitive and developed, at best, a transient arthritis. This observed difference could not be explained by a generalized lack of an inflammatory response, since we were able to elicit a zymosan peritonitis in the nude rats. However, in nude Lewis rats a striking increase in adoptively transferred AA was obtained after reconstitution with 4 x 10(8) naive syngeneic spleen cells. These combined observations suggest that a host-derived immune cell population is crucial for arthritis induction in the adoptive transfer system.