T cell regulation of collagen-induced arthritis in mice. III. Is T cell vaccination 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-Aq molecules. The clones were collagen type-specific and recognized CII from many species except the mouse. More precisely, the reactivity was directed against the immunodominant cyanogen bromide-cleaved fragment CB11(II). Analysis of the TcR carried by the T cell hybridomas showed that they used identical V alpha and J alpha (V alpha BMB, J alpha 20) gene segments and two distinct V beta (V beta 1 and V beta 4) associated with the J beta 2.5 gene segment. Interestingly, the junctional regions were highly conserved in structure and length. These findings may indicate a strong in vivo selection by the antigen for a particular combination of both alpha and beta chains of the TcR. Inoculation of irradiated anti-CII T cell hybrids into DBA/1 mice, before priming with CII, altered the course of the disease resulting in either a long-lasting suppression or an exacerbation of CIA whereas a control CD4+ hybridoma with an unrelated specificity did not influence the development of arthritis. However, the regulatory effect of anti-CII T cell clones was unpredictable, suggesting that the TcR structure may not solely account for the modulation of CIA and that T cell vaccination is not a reliable method for inducing suppression of CIA.
Chiocchia
G
G
INSERM U 283, Hôpital Cochin, Université René Descartes, Paris, France.
Manoury-Schwartz
B
B
Boissier
M C
MC
Gahery
H
H
Marche
P N
PN
Fournier
C
C
D000595:Amino Acid Sequence; D000818:Animals; D001168:Arthritis / Q000209:etiology* / Q000628:therapy; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000502:physiology*; D003094:Collagen / Q000276:immunology*; D000939:Epitopes; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006825:Hybridomas / Q000276:immunology; D016219:Immunotherapy, Adoptive; D051379:Mice; D008809:Mice, Inbred C3H; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry / Q000235:genetics
D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D016693:Receptors, Antigen, T-Cell, alpha-beta; D003094:Collagen