T-CELL REGULATION OF COLLAGEN-INDUCED ARTHRITIS IN MICE .3. IS T-CELLVACCINATION A VALUABLE THERAPY

Since T cells play a critical role in collagen-induced arthritis (CIA) , CD4(+) T cell hybridomas were derived from DBA/1 mice immunized with bovine type II collagen (CII). The hybrid clones selected were Thy-1- 2(+), CD4(+), CD8(-), T cell receptor (TcR) alpha beta(+) and produced interleukin-2 in response to CII peptides presented by I-A(q) molecul es. The clones were collagen type-specific and recognized CII from man y species except the mouse. More precisely, the reactivity was directe d against the immunodominant cyanogen bromide-cleaved fragment CB11(II ). Analysis of the TcR carried by the T cell hybridomas showed that th ey used identical V alpha and J alpha (V alpha BMB, J alpha 20) gene s egments and two distinct V beta (V beta 1 and V beta 4) associated wit h the J beta 2.5 gene segment. Interestingly, the junctional regions w ere highly conserved in structure and length. These findings may indic ate a strong in vivo selection by the antigen for a particular combina tion of both alpha and beta chains of the TcR. Inoculation of irradiat ed anti-CII T cell hybrids into DBA/1 mice, before priming with CII, a ltered the course of the disease resulting in either a long-lasting su ppression or an exacerbation of CIA whereas a control CD4(+) hybridoma with an unrelated specificity did not influence the development of ar thritis. However, the regulatory effect of anti-CII T cell clones was unpredictable, suggesting that the TcR structure may not solely accoun t for the modulation of CIA and that T cell vaccination is not a relia ble method for inducing suppression of CIA.