Experimental acute hematogenous osteomyelitis in mice. II. Influence of Staphylococcus aureus infection on T-cell immunity

A murine model of acute hematogenous osteomyelitis was used to study the im mune response following Staphylococcus aureus infection and to examine the hypothesis that the bacteria may modify T-cell responses due to the product ion of bacterial enterotoxins with mitogenic or superantigenic activity. Ly mphnode T cell-receptor expression was assessed with use of flow cytometry and reverse transcription-polymerase chain reaction techniques, and increas ed apoptosis (programmed cell death) in T-cell subsets was monitored. The e xpression and levels of circulating cytokines and T-cell cytokines within t issues surrounding the damaged area of the proximal tibia were also investi gated. Analysis of T-cell receptors in experimental osteomyelitis revealed two distinct patterns of T-cell evolution during the disease. Certain T-cel l subsets (V beta 2, V beta 3, V beta 9, and V beta 10) were activated and expanded during the first 24 hours after infection; they reached maximum le vels 6 days after infection, followed by a return to pre-infection levels. In contrast, other T-cell subsets (V beta 11, V beta 12, V beta 13, V beta 14, and V beta 16) contracted during the first 24 hours after infection, fo llowed by expansion to a maximum level 9 days after infection. Activation a nd proliferation of T-cell subsets (notably V beta 14 T cells) was followed by apoptosis, suggesting that staphylococcal bone infection caused superan tigenic-like effects on the mouse immune system. Analysis of cytokine respo nses in local tissue revealed that the T-cell cytokines interleukin-2 and i nterferon-gamma showed a late and relatively short activation pattern compa red with the inflammatory cytokines interleukin-l, interleukin-6, and tumor necrosis factor-ct. The results suggest that Staphylococcus aureus bone in fection may undermine the antibacterial immune response through downregulat ion of T-cell immunity and immune-cytokine production, which could increase the severity of the systemic infection and local osseous destruction that occur with acute hematogenous osteomyelitis.