Stochastic expansions maintain the clonal stability of CD8+ T cell populations undergoing memory inflation driven by murine cytomegalovirus

CMV is an obligate and persistent intracellular pathogen that continually drives the production of highly differentiated virus-specific CD8+ T cells in an Ag-dependent manner, a phenomenon known as memory inflation. Extensive proliferation is required to generate and maintain inflationary CD8+ T cell populations, which are counterintuitively short-lived and typically exposed to limited amounts of Ag during the chronic phase of infection. An apparent discrepancy therefore exists between the magnitude of expansion and the requirement for ongoing immunogenic stimulation. To address this issue, we explored the clonal dynamics of memory inflation. First, we tracked congenically marked OT-I cell populations in recipient mice infected with murine CMV (MCMV) expressing the cognate Ag OVA. Irrespective of numerical dominance, stochastic expansions were observed in each population, such that dominant and subdominant OT-I cells were maintained at stable frequencies over time. Second, we characterized endogenous CD8+ T cell populations specific for two classic inflationary epitopes, M38 and IE3. Multiple clonotypes simultaneously underwent Ag-driven proliferation during latent infection with MCMV. In addition, the corresponding CD8+ T cell repertoires were stable over time and dominated by persistent clonotypes, many of which also occurred in more than one mouse. Collectively, these data suggest that stochastic encounters with Ag occur frequently enough to maintain oligoclonal populations of inflationary CD8+ T cells, despite intrinsic constraints on epitope display at individual sites of infection with MCMV

Prevalence and functional impact of patient-perceived leg length discrepancy after hip replacement

The aim of this postal survey was to determine the prevalence and impact of patient-perceived leg length discrepancy (LLD) at 5–8 years after primary total hip replacement (THR). A postal audit survey was undertaken of all consecutive patients who had a primary unilateral THR at one elective orthopaedic centre between April 1993 and April 1996. The questionnaire included the Oxford hip score (OHS) and questions about LLD. Questionnaires were received from 1,114 patients. In total, 329 THR patients (30%) reported an LLD, although radiographic analysis revealed that only 36% of these patients had anatomical LLD. Patients with a perceived LLD had a significantly poorer OHS (p < 0.001) and reported more limping than those patients without a perceived LLD. This study found that a third of patients perceived an LLD after THR and that perceived LLD was associated with a significantly poorer midterm functional outcome