Theileria annulata induces abberrant T cell activation in vitro and in vivo

SUMMARY Theprotozoan parasite ofcattle, Theileria annulata, causesa severelymphoproliferative disease, developing initially inthedraining lymphnode, whichisoften fatal innaive animals. Infection of macrophages withT.annulata leads toan augmentation oftheir antigen-presenting capability invitro andinfected cells caninduce proliferation ofautologous resting Tcells fromnaive animals. Thisinappropriate activation ofT cells may play an important roleinthefailure ofthehostto mountan effective immuneresponseinvivo. To investigate thishypothesis we characterized further theresponseofT cells fromnaive cattle toinfected cells invitro, andalsoexamined the development oftheimmuneresponseinlymphnodesdraining thesites ofT.annulata infection. BothCD4+andCD8+T cells fromnaiveperipheral bloodmononuclear cells (PBMC)were induced toproliferate andexpresstheactivation markers IL-2RandMHC class IIwhencultured withinfected cells. Thiseffect was seeninboth'naive' and'memory' T cells, andwas dependent upon contact withinfected cells. Invitro, infected cells aretherefore capable ofactivating T cells irrespective oftheir antigen specificity ormemory status. Indraining lymphnodes, although large numbers ofIL-2R+cells developed following infection, these activated cells wereonlyassociated withareasofparasite-induced proliferating cells, andsubsequently disappeared fromthenode. Cells expressing IL-2Rwere notpresent inrecognized sites forT celldevelopment. Germinal centres were severely affected, losing T cell-dependent zonesfollowed bya total destruction of morphology. Tcell function istherefore severely disrupted within draining nodes. Thisstudy has shownthatparasitized cells supply sufficient signals invitro toactivate T cells irrespective of specificity. T cells also arenotstimulated inaconventional manner invivo, andthis may play an important roleinpreventing an effective immuneresponsefrombeing generated.