Exacerbation of established collagen-induced arthritis in mice treated with an anti-T cell receptor antibody.
OBJECTIVE
To investigate the effect of T cell depletion on established collagen-induced arthritis (CIA) in mice, using monoclonal antibodies (MAb) to T cell receptor alpha/beta (TCR alpha/beta). In addition, experiments using anti-CD3 MAb were performed for comparison.


METHODS
CIA was induced in male DBA/1 mice by immunizing them twice with bovine type II collagen (CII). The arthritis score and anti-CII antibody titers were examined serially. Proportions of T cells were determined by fluorescence-activated cell sorter (FACS) analysis on spleen cells or peripheral blood cells.


RESULTS
When anti-TCR alpha/beta MAb was injected on the day of CII priming, no arthritis was detected in association with depressed anti-CII antibody titers. Unexpectedly, however, when MAb was given after arthritis was established, a rapid exacerbation of arthritis was observed, which resulted in ankylosis of most joints. Anti-CII antibody titers were not affected. The addition of anti-TCR gamma/delta MAb had no effect on the augmented arthritis. T cell depletion by anti-CD3 MAb during established CIA also caused an enhancement of arthritis, which was, however, weak and only transient. FACS analysis revealed that the early improvement of arthritis after the transient augmentation seen in the mice treated with anti-CD3 MAb paralleled the early recovery of alpha/beta T cells in the periphery.


CONCLUSIONS
The present results support the concept that alpha/beta T cells, in general, may play a regulatory role in the clinical course of murine CIA after disease onset. Therefore, caution is recommended when using intensive T cell-targeted therapy in patients with rheumatoid arthritis.
Maeda
T
T
Department of Immunology, Kyushu University, Japan.
Saikawa
I
I
Hotokebuchi
T
T
Sugioka
Y
Y
Eto
M
M
Murakami
Y
Y
Nomoto
K
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001172:Arthritis, Rheumatoid / Q000139:chemically induced / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology; D003094:Collagen / Q000009:adverse effects* / Q000276:immunology; D005434:Flow Cytometry; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology; D013601:T-Lymphocytes
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D003094:Collagen