Possible role of peripheral CD14(low) monocytes in the development of collagen-induced arthritis in cynomolgus monkeys (Macaca fascicularis)

The changes in levels of peripheral major lymphocyte subsets were monitored with 10 adult cynomolgus monkeys (5 females and 5 males) during the 9 week s after immunization with chick type-ii collagen in Freund's complete adjuv ant. Three females and 3 males developed overt arthritis determined by swel ling of small joints and increase of plasma alkaline phosphatase as well as C-reactive protein. An increase of CD16(+) NK cells was observed in four n on-arthritis-developed monkeys (two females and two males). There was no si gnificant difference in the fluctuation pattern of CD4(+) T cell, CD8(+) T cell and CD20(+) B cell levels between arthritis-developed monkeys and non- developed ones. In addition, the percentages of CD45RA(+) CD4(+) T cells to total CD4(+) T cells, CD28(-) CD8(+) T cells to total CD8(+) T cells, and IgD(-) B cells to total B cells did not significantly differ between them. On the other hand, a significant increase was demonstrated in CD14-positive cells at 3 weeks after immunization in only arthritis-developed monkeys re gardless of sex. The expression of CD14 antigen on the surface of increased cells was low in comparison with those appearing in blood obtained before immunization. In addition, increased CD14(low) cells showed no response to LPS stimulation. However, there was no significant difference in antibody t iter to both chick type-ii and monkey type-ii collagen between arthritis-de veloped monkeys and non-developed ones. These results suggest that an incre ase in number of CD14(low) monocytes with immature function might be a part of the autoimmune response, and that the appearance of these cells is of p athogenic importance in the arthritic process in cynomolgus monkeys regardl ess of the production of autoantibody.