T cells from chronic bone infection show reduced proliferation and a high proportion of CD 28 − CD 4 T cells

Summary Chronic bone infection is associated with bone resorption. From animal studies, CD 3/ CD 28‐activated T cell s are known to enhance osteoclastogenesis and bone resorption. Because CD 28 is expressed constitutively on T cell s and its expression is down‐regulated by chronic exposure to the inflammatory environment, we characterized co‐stimulatory molecule expression on T cell s from chronically infected patients. We used cytofluorometric techniques to phenotypically characterize T cell s, its co‐stimulatory molecules and perforin secretion from infected and non‐infected human bones. Chronic bone infection was defined as infection lasting for more than a month. We show a higher T cell activation [human leucocyte antigen D‐related ( HLA‐DR + )] in infected compared to non‐infected bones: median being 16 versus 7%, P  = 0·009 for CD 4 T cell s, and 33 versus 15%, P  = 0·038 for CD8 T cell s, respectively. However, T cell proliferation ( K i67 + ) was lower for CD 8 T cell s in infected bones: 26 versus 34%, P  = 0·045. In contrast, we detected no difference in apoptosis and regulatory T cell s. In infected bone, we found higher CD 28‐negative CD 4 + T cell s compared to non‐infected bone: 20 versus 8%, respectively ( P  = 0·005); this T cell subset had higher CD 11b expression and perforin secretion. Chronically infected human bones are characterized by an increase of CD 28‐negative CD 4 + T cell s, indicating long‐term activated cells with cytotoxic ability. Therefore, this alteration of co‐stimulatory molecules may modify interactions with osteoclasts and impact bone resorption.