Treatment with monoclonal anti-tumor necrosis factor alpha antibody results in an accumulation of Th1 CD4+ T cells in the peripheral blood of patients with rheumatoid arthritis.
OBJECTIVE
In rheumatoid arthritis (RA), treatment with tumor necrosis factor alpha (TNFalpha) binding agents has proven to be highly effective. Downregulation of the proinflammatory cytokine cascade and a reduced migration of leukocytes into the joints have been proposed as modes of action of TNFalpha blockade. We investigated whether alterations in the number of circulating pro- and antiinflammatory T cell subsets contribute to the therapeutic effect of monoclonal antibodies (mAb) against TNFalpha in RA patients.


METHODS
Phenotypic analysis of peripheral blood T cell subsets was performed on blood from RA patients before and after treatment with an anti-TNFalpha mAb.


RESULTS
An accumulation of primed CD45RA- T cells of both the CD4+ and the CD8+ T cell population was seen shortly after treatment. Most notably, within the CD4+,CD45RA- T cell subset, the number of interferon-gamma-producing T cells was significantly increased after anti-TNFalpha mAb treatment, resulting in a significant rise in the Th1:Th2 ratio. In addition, an increase in the number of CD4+ T cells expressing the homing receptor CD49d in high density was observed after treatment, which correlated positively with the increase in the Th1:Th2 ratio. Conclusion. We show that the Th1:Th2 ratio in the peripheral blood is raised by anti-TNFalpha mAb treatment.
Maurice
M M
MM
Leiden University Medical Center, The Netherlands.
van der Graaff
W L
WL
Leow
A
A
Breedveld
F C
FC
van Lier
R A
RA
Verweij
C L
CL
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology; D005260:Female; D006801:Humans; D007167:Immunotherapy; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D014409:Tumor Necrosis Factor-alpha