Homeostasis of the naive CD4+ T cell compartment during aging

Despite thymic involution, the number of naive CD4(+) T cells diminishes slowly during aging, suggesting considerable peripheral homeostatic expansion of these cells. To investigate the mechanisms behind, and consequences of, naive CD4+ T cell homeostasis, we evaluated the age-dependent dynamics of the naive CD4+ T cell subsets CD45RA+CD31+ and CD45RA+CD31-. Using both a cross-sectional and longitudinal study design, we measured the relative proportion of both subsets in individuals ranging from 22 to 73 years of age and quantified TCR excision circle content within those subsets as an indicator of proliferative history. Our findings demonstrate that waning thymic output results in a decrease in CD45RA+CD31+ naive CD4+ T cells over time, although we noted considerable individual variability in the kinetics of this change. In contrast, there was no significant decline in the CD45RA+CD31- naive CD4+ T cell subset due to extensive peripheral proliferation. Our longitudinal data are the first to demonstrate that the CD45RA+CD31+CD4+ subset also undergoes some in vivo proliferation without immediate loss of CD31, resulting in an accumulation of CD45RA+CD31+ proliferative offspring. Aging was associated with telomere shortening within both subsets, raising the possibility that accumulation of proliferative offspring contributes to senescence of the naive CD4+ T cell compartment in the elderly. In contrast, we observed retention of clonal TCR diversity despite peripheral expansion, although this analysis did not include individuals over 65 years of age. Our results provide insight into naive CD4+ T cell homeostasis during aging that can be used to better understand the mechanisms that may contribute to immunosenescence within this compartment.     

AIDS restriction HLA allotypes target distinct intervals of HIV-1 pathogenesis

An effective acquired immune response to infectious agents mediated by HLA-restricted T-cell recognition can target different stages of disease pathogenesis. We show here that three distinct HLA alleles known to alter the overall rate of AIDS progression act during distinct intervals after HIV-1 infection. The discrete timing of HLA allele influence suggests alternative functional mechanisms in immune defense against this dynamic and chronic immunosuppressive disease.     

ACUTE EFFECTS OF MOVEMENT VELOCITY ON BLOOD LACTATE AND GROWTH HORMONE RESPONSES AFTER ECCENTRIC BENCH PRESS EXERCISE IN RESISTANCE-TRAINED MEN

This study aimed to compare the effects of different velocities of eccentric muscle actions on acute blood lactate and serum growth hormone (GH) concentrations following free weight bench press exercises performed by resistance-trained men. Sixteen healthy men were divided into two groups: slow eccentric velocity (SEV; n = 8) and fast eccentric velocity (FEV; n = 8). Both groups performed four sets of eight eccentric repetitions at an intensity of 70% of their one repetition maximum eccentric (1RMecc) test, with 2-minute rest intervals between sets. The eccentric velocity was controlled to 3 seconds per range of motion for SEV and 0.5 seconds for the FEV group. There was a significant difference (P < 0.001) in the kinetics of blood lactate removal (at 3, 6, 9, 15, and 20 min) and higher mean values for peak blood lactate (P = 0.001) for the SEV group (9.1 ± 0.5 mM) compared to the FEV group (6.1 ± 0.4 mM). Additionally, serum GH concentrations were significantly higher (P < 0.001) at 15 minutes after bench press exercise in the SEV group (1.7 ± 0.6 ng · mL⁻¹) relative to the FEV group (0.1 ± 0.0 ng · mL⁻¹). In conclusion, the velocity of eccentric muscle action influences acute responses following bench press exercises performed by resistance-trained men using a slow velocity resulting in a greater metabolic stress and hormone response.     

Cellular calcium and atherosclerosis: A brief review

Evidence for and against the theory that cell calcium is causally involved in the pathogenesis of atherosclerosis is presented and evaluated. In particular, it is argued that: (1) arterial calcium is increased in atherosclerosis; (2) this increase in tissue calcium content is largely intracellular; (3) this increased intracellular calcium content is caused by increased plasma membrane calcium permeability; (4) the increased calcium content is causally related to atherogenesis; (5) many of the cell physiological, cell biological, biochemical, and molecular biological processes, known to function abnormally in atherosclerosis, are also known to be calcium regulated; and (6) these processes are activated or inactivated in atherosclerosis in a manner consistent with increased cell calcium. It is concluded that the calcium-atherogenesis hypothesis has the potential to unify macroscopic clinical risk factors in terms of intracellular mechanisms that are controlled by cell calcium, and that this hypothesis deserves further experimental tests.     

Recommendations for Reporting and Flagging of Reference Limits on Pathology Reports

Surveys by the RCPA PITUS Project have shown significant variations in report rendering between Australasian Pathology Providers. The same project collected anecdotal evidence that this variation has led to the misunderstanding and misreading of results - a clinical safety issue. Recommendations are given for the rendering of reference limits on pathology reports, determination and rendering of result flags, and the documentation of sub-population partitions for reference intervals. These recommendations apply equally for paper or electronic reporting, but should not limit the use of novel techniques within electronic reports to convey additional meaning. PITUS Working Group 4 will publish draft recommendations for peer review and comment in relation to the above in the second half of 2014.