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The aim of this study was to assess the effects in humans of early (2 weeks) and delayed (6 weeks) isokinetic strength training in the recovery of muscle strength following an arthroscopic partial meniscectomy. The peak torque developed in the quadriceps and hamstrings and the torque developed at a knee angle of 1.05 rad were evaluated in 16 subjects, pre-operatively (pre-op), and 2, 6, and 10 weeks post-operatively (post-op), on an isokinetic device at four different velocities (1.05, 2.09, 3.14, and 4.19 rad.s-1). The fatigue characteristics of the muscles were evaluated by having the subject perform 15 maximal contractions at 3.14 rad.s-1. Training was done on the same device (three times a week for 1-2 months), beginning either 2 or 6 weeks post-op. A repeated measures analysis of variance demonstrated a time effect but no differences between groups and no interactions. Torques developed by the knee flexors and extensors were significantly smaller 2 weeks post-op than pre-op, at all velocities tested. Torques developed in the quadriceps recovered to their pre-op values by 6 weeks, and further gained significantly in strength from 6 to 10 weeks. Quadriceps torques remained weaker than the contralateral side at 10 weeks. Hamstrings torques were either higher or similar to pre-op values by 6 weeks, and demonstrated increases from 6 to 10 weeks post-op at 1.05 and 4.19 rad.s-1 only. Total work and average power developed by the quadriceps and hamstrings during the fatigue protocol changed with time in a similar manner to torque.(ABSTRACT TRUNCATED AT 250 WORDS)

The CD45 protein tyrosine phosphatase regulates Ag receptor signaling in T and B cells. In the absence of CD45, TCR coupling to downstream signaling cascades is profoundly reduced. Moreover, in CD45-null mice, the maturation of CD4+CD8+ thymocytes into CD4+CD8− or CD4−CD8+ thymocytes is severely impaired. These findings suggest that thymic selection may not proceed normally in CD45-null mice, and may be biased in favor of thymocytes expressing TCRs with strong reactivity toward self-MHC-peptide ligands to compensate for debilitated TCR signaling. To test this possibility, we purified peripheral T cells from CD45-null mice and fused them with the BWα−β− thymoma to generate hybridomas expressing normal levels of TCR and CD45. The reactivity of these hybridomas to self or foreign MHC-peptide complexes was assessed by measuring the amount of IL-2 secreted upon stimulation with syngeneic or allogeneic splenocytes. A very high proportion (55%) of the hybridomas tested reacted against syngeneic APCs, indicating that the majority of T cells in CD45-null mice express TCRs with high avidity for self-MHC-peptide ligands, and are thus potentially autoreactive. Furthermore, a large proportion of TCRs selected in CD45-null mice (H-2b) were also shown to display reactivity toward closely related MHC-peptide complexes, such as H-2bm12. These results support the notion that modulating the strength of TCR-mediated signals can alter the outcome of thymic selection, and demonstrate that CD45, by molding the window of affinity/avidity for positive and negative selection, directly participates in the shaping of the T cell repertoire.

We report a novel in vitro approach that allows study of the consequences of TCR ligation on thymocytes in the absence of thymic stromal cells. Hence, thymocytes were incubated either in the presence of recombinant antigenic peptide/MHC complexes, which represent ligands of physiologic affinities, or with anti-TCR mAb, a ligand of supraphysiologic affinity. Whereas TCR cross-linking with mAb led to thymocyte deletion, incubation with peptide/MHC ligands did not trigger cellular apoptosis. However, the addition of a costimulatory signal (provided by anti-CD28 mAb) allowed the induction of apoptosis following TCR binding to peptide/MHC ligands, and it increased the levels of cell death obtained through mAb-mediated TCR cross-linking. Requirement for accessory signals seen with TCR stimulation by peptide/MHC complexes argues in favor of qualitative differences between TCR engagement by ligands of either physiologic or supraphysiologic affinity.

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