A ROLE FOR CD8(-LYMPHOCYTES IN OSTEOCLAST DIFFERENTIATION IN-VITRO() T)

Bone loss associated with chronic inflammatory diseases has been attri buted to the release of cytokines from T lymphocytes. However, the rol e of T lymphocyte subsets in the mediation of osteoclast activity has not been extensively studied. Cocultures of murine bone marrow and BAL C cells (murine calvarial-derived cell line) were used to study osteoc last differentiation. Murine marrow was left intact or depleted of cel ls expressing the CD8 or CD4 antigen by immunomagnetic separation and then cocultured with BALC cells in the presence or absence of 1,25-(OH )(2)D-3. Depleting bone marrow of CD4-positive (CD4(+)) cells did not affect osteoclast differentiation (formation of nuclei). However, depl etion of CD8-positive (CD8(+)) cells resulted in a 40% increase in the number of osteoclasts formed. Addition of CD8(+) cells to CD8(+) cell depleted cocultures via Transwells abolished the stimulatory effects on osteoclast differentiation resulting from CD8(+) cell depletion. Ne utralizing antibodies to interleukin-4 and transforming growth factor- beta did not affect osteoclast differentiation in these cultures. Thes e findings suggest that CD8(+) cells may be involved in the regulation of osteoclast differentiation and that this effect is not mediated by interleukin-4 or transforming growth factor-beta.