title: T cells from chronic bone infection show reduced proliferation and a high proportion of CD28⁻ CD4 T cells.
abstract: Chronic bone infection is associated with bone resorption. From animal studies, CD3/CD28-activated T cells are known to enhance osteoclastogenesis and bone resorption. Because CD28 is expressed constitutively on T cells and its expression is down-regulated by chronic exposure to the inflammatory environment, we characterized co-stimulatory molecule expression on T cells from chronically infected patients. We used cytofluorometric techniques to phenotypically characterize T cells, 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 CD4 T cells, and 33 versus 15%, P = 0·038 for CD8 T cells, respectively. However, T cell proliferation (Ki67⁺) was lower for CD8 T cells in infected bones: 26 versus 34%, P = 0·045. In contrast, we detected no difference in apoptosis and regulatory T cells. In infected bone, we found higher CD28-negative CD4⁺ T cells compared to non-infected bone: 20 versus 8%, respectively (P = 0·005); this T cell subset had higher CD11b expression and perforin secretion. Chronically infected human bones are characterized by an increase of CD28-negative CD4⁺ T cells, indicating long-term activated cells with cytotoxic ability. Therefore, this alteration of co-stimulatory molecules may modify interactions with osteoclasts and impact bone resorption.
authors.affiliation: Unité 576, Institut National de la Santé et de la Recherche Médicale, Hopital L'Archet 1, Centre Hospitalier Universitaire de Nice, Université de Nice Sophia-Antipolis, Nice, France.
authors.forename: G
authors.initials: G
authors.lastname: Kumar
authors.forename: P-M
authors.initials: PM
authors.lastname: Roger
authors.forename: M
authors.initials: M
authors.lastname: Ticchioni
authors.forename: C
authors.initials: C
authors.lastname: Trojani
authors.forename: R
authors.initials: R
authors.lastname: Bernard de Dompsur
authors.forename: N
authors.initials: N
authors.lastname: Bronsard
authors.forename: M
authors.initials: M
authors.lastname: Carles
authors.forename: E
authors.initials: E
authors.lastname: Bernard
mesh_terms: D000328:Adult; D000368:Aged; D001424:Bacterial Infections / Q000097:blood / Q000276:immunology*; D018106:CD28 Antigens / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation; D002908:Chronic Disease; D005260:Female; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D010019:Osteomyelitis / Q000097:blood / Q000276:immunology*; D054353:Perforin / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors; D055815:Young Adult
chemical_list: D018106:CD28 Antigens; D006684:HLA-DR Antigens; D054353:Perforin
keywords: T cells; apoptosis; bacterial; cell proliferation; regulatory T cells