Abstract
BackgroundAnterior cruciate ligament (ACL) and meniscus tears are common knee injuries. Despite the high rate of post-traumatic osteoarthritis (PTOA) following these injuries, the contributing factors remain unclear. In this study, we characterized the immune cell profiles of normal and injured joints at the time of ACL and meniscal surgeries.MethodsTwenty-nine patients (14 meniscus-injured and 15 ACL-injured) undergoing ACL and/or meniscus surgery but with a normal contralateral knee were recruited. During surgery, synovial fluid was aspirated from both normal and injured knees. Synovial fluid cells were pelleted, washed, and stained with an antibody cocktail consisting of fluorescent antibodies for cell surface proteins. Analysis of immune cells in the synovial fluid was performed by polychromatic flow cytometry. A broad spectrum immune cell panel was used in the first 10 subjects. Based on these results, a T cell-specific panel was used in the subsequent 19 subjects.ResultsUsing the broad spectrum immune cell panel, we detected significantly more total viable cells and CD3 T cells in the injured compared to the paired normal knees. In addition, there were significantly more injured knees with T cells above a 500-cell threshold. Within the injured knees, CD4 and CD8 T cells were able to be differentiated into subsets. The frequency of total CD4 T cells was significantly different among injury types, but no statistical differences were detected among CD4 and CD8 T cell subsets by injury type.ConclusionsOur findings provide foundational data showing that ACL and meniscus injuries induce an immune cell-rich microenvironment that consists primarily of T cells with multiple T helper phenotypes. Future studies investigating the relationship between immune cells and joint degeneration may provide an enhanced understanding of the pathophysiology of PTOA following joint injury.
Highlights
Anterior cruciate ligament (ACL) and meniscus tears are common knee injuries
Delineation of synovial fluid T cell subsets In a separate group of 19 subjects with ACL and/or meniscus tears (Table 4), we focused our analysis on identifying T cell subsets that are recruited to the synovial fluid following knee injury
These phenotypes are similar to Th cells found in subjects with advanced OA and rheumatoid arthritis (RA) [33, 35, 41], suggesting that these immune cells may be important mediators of joint changes after ACL and meniscus injuries that contribute to post-traumatic osteoarthritis (PTOA) development
Summary
Anterior cruciate ligament (ACL) and meniscus tears are common knee injuries. Despite the high rate of post-traumatic osteoarthritis (PTOA) following these injuries, the contributing factors remain unclear. Anterior cruciate ligament (ACL) ruptures and meniscal tears are common among athletes, and frequently occur in the general population [1]. The long-term sequelae of both ACL and meniscal injuries include pain, joint instability, and post-traumatic osteoarthritis (PTOA) in approximately 50% of patients [1, 4,5,6,7]. Despite the high rate of PTOA following joint injury, the factors that contribute to PTOA development remain unclear. Other studies suggest that biological changes [19,20,21,22,23,24] that occur within the joint following injury may play a role in PTOA development as well. There is little data on the biochemical and cellular environment of the joint following injury
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