Targeting age‐specific changes in CD4+ T cell metabolism ameliorates alloimmune responses and prolongs graft survival

Age impacts alloimmunity. Effects of aging on T‐cell metabolism and the potential to interfere with immunosuppressants have not been explored yet. Here, we dissected metabolic pathways of CD4⁺ and CD8⁺ T cells in aging and offer novel immunosuppressive targets. Upon activation, CD4⁺ T cells from old mice failed to exhibit adequate metabolic reprogramming resulting into compromised metabolic pathways, including oxidative phosphorylation (OXPHOS) and glycolysis. Comparable results were also observed in elderly human patients. Although glutaminolysis remained the dominant and age‐independent source of mitochondria for activated CD4⁺ T cells, old but not young CD4⁺ T cells relied heavily on glutaminolysis. Treating young and old murine and human CD4⁺ T cells with 6‐diazo‐5‐oxo‐l‐norleucine (DON), a glutaminolysis inhibitor resulted in significantly reduced IFN‐γ production and compromised proliferative capacities specifically of old CD4⁺ T cells. Of translational relevance, old and young mice that had been transplanted with fully mismatched skin grafts and treated with DON demonstrated dampened Th1‐ and Th17‐driven alloimmune responses. Moreover, DON diminished cytokine production and proliferation of old CD4⁺ T cells in vivo leading to a significantly prolonged allograft survival specifically in old recipients. Graft prolongation in young animals, in contrast, was only achieved when DON was applied in combination with an inhibition of glycolysis (2‐deoxy‐d‐glucose, 2‐DG) and OXPHOS (metformin), two alternative metabolic pathways. Notably, metabolic treatment had not been linked to toxicities. Remarkably, immunosuppressive capacities of DON were specific to CD4⁺ T cells as adoptively transferred young CD4⁺ T cells prevented immunosuppressive capacities of DON on allograft survival in old recipients. Depletion of CD8⁺ T cells did not alter transplant outcomes in either young or old recipients. Taken together, our data introduce an age‐specific metabolic reprogramming of CD4⁺ T cells. Targeting those pathways offers novel and age‐specific approaches for immunosuppression.     

Reproduction rates and secondary production of three species of the rotifer genus Synchaeta in the estuarine Potomac River

Rotifers are a relatively well-studied component of lacustrinesystems but their role is only poorly understood in estuaries.Three species of the genus Synchaeta—S. baltica, S. triophthalmaand S.cecilia—dominate the cold-water assemblage of rotifersin Chesapeake Bay. Laboratory experiments were conducted todetermine the temperature dependence of egg development time(EDT) for each species; EDT varied over an approximate rangeof 90–9 h as temperature (T) varied from 2 to 22°C.The EDT/temperature relationships could be closely fitted bya simple polynomial equation of the form log(EDT) = a + b(logT) + c(log T)² for each species. Natural populations of thesethree rotifers were sampled during a cruise in the Potomac River(7–11 March 1983). Estimates of specific reproductiverates (b) were calculated based on the previously defined EDT/temperaturerelationship and the observed ratio of eggs/rotifers for eachspecies. The two most abundant species, S.triophthalma and S.cecilia,showed a clear dependence of b on the observed chlorophyll aconcentrations. Maximum reproductive rates ({small tilde}0.015h^–1) were attained only at relatively high phytoplanktondensities within a bloom of Heterocapsa triquetra where thechlorophyll a concentrations exceeded 10 µg l^–1.Estimates of secondary production suggest that Synchaeta spp.may contribute to the trophic flow of carbon in this systemwith a significance at least similar to that of the planktoniccopepods.     

OCCURRENCE OF RICHELIA INTACELLULARIS (CYANOPHYTA)WITHIN THE DIATOMMMS HEMIAULUS HAUKII ADN H. MEMBRANACEUS OFF HAWAII1

The presence of nitrogen–Fixing cyanobacterial endophytes, such as Richelia intracellularis Schmidit commonly observed within several species of Rhizosolenia, in nitrogen-limited oceanic waters has obvious implications both for the host organism(s) and for the entire planktonic assemblage. Recently, epi-fluorescent examination of pllankton samples collected off Oahu, Hawaii, in september 1982 revealed R. intracellularis within the diatoms Hemiaulus membranaceus Cleve and H. hauckii Grunow as well as its expected presence within Rhizosolennia spp. Richelia intracellularis coccurred with within Hemiaulus spp. at frequenccies (ca.80%)comparable to those noted for Rhizosolenia spp. Standard bright field or phaseconrast microsocopy could not reliably distinguish the cyanobacteria within Hemiaulus spp. If this association is common, the occurrence of R.intracellularis (and its significance in the nitrogen dynamics of the ocean)may have been greatly underestimated in previous studies.     

Possible consequences of containing microplankton for physiological rate measurements

Ten experiments were done in oligotrophic North Pacific waters to examine the effects of small-volume, short-period containment (6–24 h) on plankton and their implications for productivity measurements. Effects of pre-filtering samples were also considered. Chlorophyll α and adenosine triphosphate were measured, but the major emphasis was on changes in the taxonomic composition and abundance of the microplankton.Chlorophyll α measurements indicate the variability of replicate samples increased significantly during incubation; the coefficient of variation of duplicate productivity measurements ranged between 3 % and 40 %. A large fraction of this may be due to increasing heterogeneity of the phytoplankton during incubation.Pre-filtering samples through 202, 102, 35 and 15μm mesh filters removed a small but consistent fraction of phytoplankton (as estimated by chlorophyll α) but a highly variable amount of total biomass (as estimated by ATP). The effect of pre-filtration on primary production was very inconsistent between experiments, varying both in magnitude and direction.The composition of the contained microplankton changed markedly during incubation. Nearly all components decreased in abundance regardless of pre-filtration treatment and some ciliate groups completely disappeared.     

The myoglobin of primates: the Night Monkey, Aotes trivirgatus (Cebidae,Platyrrhini, Anthropoidea)

The amino acid sequence of the myoglobin of the South American Night Monkey, Aotes trivirgatus, is identical to that of the marmoset (Callithrix jacchus [1]) except for residue 21 which is isoleucine in the marmoset, like in all other anthropoids, but valine in Aotes. Analysis of a possible pathway of the evolution of Aotes myoglobin using 18 known primate myoglobin sequences [2–5] supports the classification of the Night Monkey within Anthropoidea and Platyrrhini but it indicates that this species might be more closely related to the marmoset (family Callitrichidae) than to the family Cebidae as a member of which it is commonly classified.