Recent studies have suggested a possible role of T-cells and tumor necrosis factor-alpha (TNF-alpha) in the pathogenesis of bone loss which occurs in systemic inflammatory diseases. The relevance of T-cells activity in bone loss due to estrogen deficiency has been investigated in recent years by Dr. Pacifici's group. They have shown that the increased presence of TNF-alpha producing T-cells is essential for the changes in bone metabolism during estrogen deficiency. Lack of estrogen increases interferon-y (INF-y) production by helper T-cells, which through complex class II an increased expression of major histocompatibility complex class II (MCHII) on antigen presenting cells, enhances the activation and proliferation of TNF-alpha producing T-cells. The protective role of estrogen on bone loss is mediated by type beta transforming growth factor (TGF-beta), which blocks T-cell activation and T-cell TNF-alpha production by repressing antigen presentation.