Cellmigration studies intheadoptive transfer ofadjuvant arthritis intheLewisrat

&SUMMARY Adjuvant arthritis (AA)can beinduced inLewisratsbya single injection ofeither heat-killed Mycobacterium tuberculosis orthelipoidal amineCP20961. Concanavalin A (ConA)-stimulated T cells isolated fromAA rats areable toadoptively transfer thedisease tonaive syngeneic recipients. It isunclear, however, whether these transferred cells traffic directly tothejoint andinitiate arthritis, or whether secondary hostcells areresponsible foractivation ofthedisease. Inthecurrentinvestigation, Tcells labelled withthevital fluorescent dyesHoechst H33342andZynaxis PKH26-Gwere usedto adoptively transfer adjuvant disease tonaive recipients. Atvarious stagesofdisease development sections ofankle joints, together witha range ofsofttissues, were examined byfluorescence microscopy todetermine thedistribution oflabelled donorcells intherecipients. Intensely fluorescent lymphocytes wereobserved intheliver, spleen andlymphnodes within 24hrofadoptive transfer. Fociofsuchcells wereclearly visible intheprimary lymphoid tissues aslate as14daysafter transfer. However, closeexamination ofbothanklejoint sections andpatellar fatpadcells throughout thetime-course ofthestudy failed todetect anylabelled cells atthelesion site. Todevelop these observations further, we performed adoptive transfers tonudeLewis rats(rnu/rnu) andfound thatthey wereonlymoderately sensitive anddeveloped, atbest, atransient arthritis. Thisobserved difference could notbeexplained byageneralized lackofan inflammatory response,since we were able toelicit azymosanperitonitis inthenuderats. However, innudeLewis rats astriking increase in adoptively transferred AA was obtained after reconstitution with4x I0Onaive syngeneic spleen cells. Thesecombined observations suggest that a host-derived immunecell population iscrucial for arthritis induction intheadoptive transfer system.