Reducing the level of nutrition of twin-bearing ewes during mid to late pregnancy produces leaner prime lambs at slaughter.

The Australian prime lamb industry is seeking to improve lean meat yield (LMY) as a means to increasing efficiency and profitability across the whole value chain. The LMY of prime lambs is affected by genetics and on-farm nutrition from birth to slaughter and is the total muscle weight relative to the total carcass weight. Under the production conditions of south eastern Australia, many ewe flocks experience a moderate reduction in nutrition in mid to late pregnancy due to a decrease in pasture availability and quality. Correcting nutritional deficits throughout gestation requires the feeding of supplements. This enables the pregnant ewe to meet condition score (CS) targets at lambing. However, limited resources on farm often mean it is difficult to effectively manage nutritional supplementation of the pregnant ewe flock. The impact of reduced ewe nutrition in mid to late pregnancy on the body composition of finishing lambs and subsequent carcass composition remains unknown. This study investigated the effect of moderately reducing ewe nutrition in mid to late gestation on the body composition of finishing lambs and carcass composition at slaughter on a commercial scale. Multiple born lambs to CS2.5 target ewes were lighter at birth and weaning, had lower feedlot entry and exit weights with lower pre-slaughter and carcass weights compared with CS3.0 and CS3.5 target ewes. These lambs also had significantly lower eye muscle and fat depth when measured by ultrasound prior to slaughter and carcass subcutaneous fat depth measured 110 mm from the spine along the 12th rib (GR 12th) and at the C-site (C-fat). Although carcasses were ~5% lighter, results showed that male progeny born to ewes with reduced nutrition from day 50 gestation to a target CS2.5 at lambing had a higher percentage of lean tissue mass as measured by dual energy X-ray absorptiometry and a lower percentage of fat during finishing and at slaughter, with the multiple born progeny from CS3.0 and CS3.5 target ewes being similar. These data suggest lambs produced from multiple bearing ewes that have had a moderate reduction in nutrition during pregnancy are less mature. This effect was also independent of lamb finishing system. The 5% reduction in carcass weight observed in this study would have commercially relevant consequences for prime lamb producers, despite a small gain in LMY.

A disintegrin and metalloprotease-12 is type I myofiber specific in Bos taurus and Bos indicus cattle.

A disintegrin and metalloproteinase-12 (ADAM12) is involved in the regulation of myogenesis and adipogenesis and is of interest as a potential target to manipulate skeletal muscle development and intramuscular fat (IMF) deposition in cattle to increase beef yield and improve meat quality. The longissimus thoracis muscle (LM) and semitendinosus muscle (STM) from 5 Bos taurus (Angus) and 5 Bos indicus (Brahman) cattle were collected for histological and ADAM12 gene and protein expression analysis. Myofiber typing was used to determine if ADAM12 expression patterns related to differences in muscling and IMF deposition, which are influenced by proportions of the different myofiber types. The STM was found to contain a higher proportion of glycolytic myofibers than the LM, which contained a greater proportion of oxidative myofibers (myofiber ratio of glycolytic to more oxidative types in LM and STM of 1.1 and 3.5, respectively; P < 0.05). ADAM12 gene expression, fluorescent immunohistochemical staining for ADAM12, and image analysis found ADAM12 to be greater in the LM (P < 0.05). Regression analysis found a strong, positive relationship for the distribution of ADAM12 against the proportion of type I myofibers (P < 0.05, r(2) = 0.86). These findings suggest ADAM12 is upregulated in muscles with more slow-oxidative myofibres, such as the LM, and is linked to type I myofibers in cattle. ADAM12 may be important in the regulation and maintenance slow myofibers in the LM muscle.

Associations of sire estimated breeding values and objective meat quality measurements with sensory scores in Australian lamb.

The impact of selecting for lean meat yield using breeding values for increased eye muscle depth (PEMD) and decreased fat depth (PFAT) on the consumer acceptance of lamb meat was evaluated. Consumer sensory scores (tenderness, juiciness, flavour, odour, overall liking) were obtained for the longissimus lumborum (loin) and semimembranosus (topside) muscles of 1471 lambs. On average loin samples were more acceptable for consumers. Sensory scores increased with higher IMF levels, with lower shear force levels, and when animals were younger and less muscular. Increasing PEMD decreased tenderness, overall liking and flavour scores in both muscles, and decreasing PFAT reduced tenderness within the loin samples only. This negative impact of PEMD and PFAT is not solely driven through the phenotypic impact of IMF and shear force on sensory scores. Our results confirm the growing concerns that selecting for lean meat yield would reduce consumer eating quality, and highlight that careful monitoring of selection programmes is needed to maintain lamb eating quality.

Lack of association between allelic status and myostatin content in lambs with the myostatin g+6723G>A allele.

Lambs with the myostatin (MSTN) g+6723G>A mutation have a greater muscle mass, which is believed to be associated with reduced myostatin protein abundance. This experiment was designed to determine if differences in allelic frequency of the MSTN g+6723G>A mutation affected abundance of myostatin protein from birth to 24 wk of age. A Poll Dorset cross White Suffolk ram (MSTN A/G) was mated to 35 White Suffolk cross Border Leicester cross Merino ewes (MSTN A/G, n=21, and MSTN G/G, n=14). The progeny of these matings delivered 44 lambs with MSTN A/A (n=9), MSTN A/G (n=21), and MSTN G/G (n=14) genotypes. At approximately 1, 4, and 12 wk of age, a biopsy sample was collected and a blood sample was taken to measure the abundance of myostatin protein in muscle and plasma. At approximately 24 wk of age, the wether lambs were slaughtered to determine carcass characteristics and muscle samples were taken from the bicep femoris. The abundance of mature myostatin protein in muscle from 1 wk old lambs was less (P=0.05) in MSTN A/A and MSTN A/G compared with MSTN G/G lambs. However, at 4 and 24 wk the MSTN A/A lambs had a greater (P=0.04) abundance of myostatin protein compared with the MSTN A/G and MSTN G/G lambs. The abundance of mature myostatin did not differ between genotypes in plasma but the myostatin protein did increase as the lambs aged. At slaughter the MSTN A/A wether lambs had greater dressing percentages (P=0.04), shortloin (P=0.01), topside (P<0.001), and round (P=0.01) weights but did not differ in final BW or HCW (P>0.05). The MSTN A/A lambs had more muscle fibers (P=0.02) in the cross-section of LM between the 12th and 13th rib. The MSTN A/A lambs also had greater lean (P=0.002), less fat (P=0.009), and reduced organ (heart, liver, spleen, and kidneys) mass as determined by computed tomography scanning than MSTN G/G lambs. The results of this study demonstrated that lambs homozygous for the MSTN g+6723G>A mutation have changes in carcass characteristics (dressing and total lean), organ weights, and muscle fiber number. This may be due to reduced myostatin protein early in utero, but after 4 wk of age there was no difference in the abundance of mature myostatin protein in muscle or plasma among MSTN A/A, MSTN A/G, and MSTN G/G genotypes.

Methodology for the development of antithrombotic therapy and prevention of thrombosis guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines

BACKGROUND: To develop the Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: ACCP Evidence-Based Clinical Practice Guidelines (AT9), the American College of Chest Physicians (ACCP) assembled a panel of clinical experts, information scientists, decision scientists, and systematic review and guideline methodologists. METHODS: Clinical areas were designated as articles, and a methodologist without important intellectual or financial conflicts of interest led a panel for each article. Only panel members without significant conflicts of interest participated in making recommendations. Panelists specified the population, intervention and alternative, and outcomes for each clinical question and defined criteria for eligible studies. Panelists and an independent evidence-based practice center executed systematic searches for relevant studies and evaluated the evidence, and where resources and evidence permitted, they created standardized tables that present the quality of the evidence and key results in a transparent fashion. RESULTS: One or more recommendations relate to each specific clinical question, and each recommendation is clearly linked to the underlying body of evidence. Judgments regarding the quality of evidence and strength of recommendations were based on approaches developed by the Grades of Recommendations, Assessment, Development, and Evaluation Working Group. Panel members constructed scenarios describing relevant health states and rated the disutility associated with these states based on an additional systematic review of evidence regarding patient values and preferences for antithrombotic therapy. These ratings guided value and preference decisions underlying the recommendations. Each topic panel identified questions in which resource allocation issues were particularly important and, for these issues, experts in economic analysis provided additional searches and guidance. CONCLUSIONS: AT9 methodology reflects the current science of evidence-based clinical practice guideline development, with reliance on high-quality systematic reviews, a standardized process for quality assessment of individual studies and the body of evidence, an explicit process for translating the evidence into recommendations, disclosure of financial as well as intellectual conflicts of interest followed by management of disclosed conflicts, and extensive peer review.(AU)

Extended safety and efficacy studies of the attenuated Brucella vaccine candidates 16 M(Delta)vjbR and S19(Delta)vjbR in the immunocompromised IRF-1-/- mouse model.

The global distribution of brucellosis and high incidence in certain areas of the world warrant the development of a safer and efficacious vaccine. For the past 10 years, we have focused our attention on the development of a safer, but still highly protective, live attenuated vaccine for human and animal use. We have demonstrated the safety and protective efficacy of the vaccine candidates 16 MΔvjbR and S19ΔvjbR against homologous and heterologous challenge in multiple immunocompetent animal models, including mice and deer. In the present study, we conducted a series of experiments to determine the safety of the vaccine candidates in interferon regulatory factor-1-knockout (IRF-1(-/-)) mice. IRF-1(-/-) mice infected with either wild-type Brucella melitensis 16 M or the vaccine strain Brucella abortus S19 succumb to the disease within the first 3 weeks of infection, which is characterized by a marked granulomatous and neutrophilic inflammatory response that principally targets the spleen and liver. In contrast, IRF-1(-/-) mice inoculated with either the 16 MΔvjbR or S19ΔvjbR vaccine do not show any clinical or major pathological changes associated with vaccination. Additionally, when 16 MΔvjbR- or S19ΔvjbR-vaccinated mice are challenged with wild-type Brucella melitensis 16M, the degree of colonization in multiple organs, along with associated pathological changes, is significantly reduced. These findings not only demonstrate the safety and protective efficacy of the vjbR mutant in an immunocompromised mouse model but also suggest the participation of lesser-known mechanisms in protective immunity against brucellosis.

Myostatin allelic status interacts with level of nutrition to affect growth, composition, and myofiber characteristics of lambs.

The objective of this experiment was to determine if growth, carcass composition, and myofiber characteristics of lambs were affected by heterozygosity for a myostatin mutation (g+6723G>A) when offered differing allowances of feed administered with or without ractopamine. Heterozygote [MSTN A/G (n = 40)] and homozygote wildtype [MSTN G/G (n = 39)] castrate male lambs were individually fed ad libitum (HI; 1.8 × estimated ME(m)) or a restricted allowance (LO; 1.1 × estimated ME(m)) of a diet (191 g of CP/kg of DM and 12 MJ of ME/kg of DM), supplemented with (0.4 mg/kg of BW) or without the ß-adrenergic agonist ractopamine (RAC or NO RAC) for 47 d. The lambs were scanned by computed tomography at the beginning and completion of the feeding experiment to calculate composition of lean, fat, and bone in the carcass component of the body. The MSTN A/G HI intake lambs had significantly greater total daily carcass growth (P = 0.045) and loin eye depth (P = 0.022) and tended to have a greater daily growth of lean (P = 0.09) in the carcass, compared with MSTN G/G HI intake lambs. Conversely, MSTN A/G LO intake lambs tended to have less daily lean deposition (P = 0.09), significantly less total daily carcass growth (P = 0.045), and had a greater percentage of type IIX myofibers (P < 0.01) and total myofiber area (relative area) of type IIX myofibers (P = 0.013). The inclusion of RAC increased final BW (P = 0.03) and ADG (P = 0.02), percentage of type IIC (P < 0.001) and IIA (P = 0.012) myofibers, cross-sectional area of types I (P = 0.04) and IIAX (P = 0.04) fibers, and the relative area of type IIC (P = 0.003) and IIA (P = 0.01) myofibers in the LM. The experiment demonstrated that including RAC in the diet of lambs increased final BW and ADG, but not HCW, and increased proportion of type IIC and IIA myofibers and cross-sectional area of type I and IIAX myofibers. Our data suggest that RAC and the heterozygous myostatin mutation act together to increase growth of muscle on a high plane of nutrition. The experiment also demonstrated that poor nutritional background of lambs heterozygous for the myostatin mutation may negatively influence their growth rates and myofiber characteristics.

Protective efficacy and safety of Brucella melitensis 16MΔmucR against intraperitoneal and aerosol challenge in BALB/c mice.

Brucellosis is a zoonosis of nearly worldwide distribution. Vaccination against this pathogen is an important control strategy to prevent the disease. Currently licensed vaccine strains used in animals are unacceptable for human use due to undesirable side effects and modest protection. Substantial progress has been made during the past 10 years toward the development of improved vaccines for brucellosis. In part, this has been achieved by the identification and characterization of live attenuated mutants that are safer in the host but still can stimulate an adequate immune response. In the present study, the identification and characterization of the mucR mutant (BMEI 1364) as a vaccine candidate for brucellosis was conducted. BALB/c mice were vaccinated intraperitoneally at a dose of 10(5) CFU with the mutant to evaluate safety and protective efficacy against intraperitoneal and aerosol challenge. All animals vaccinated with the vaccine candidate demonstrated a statistically significant degree of protection against both intraperitoneal and aerosol challenge. Safety was revealed by the absence of Brucella associated pathological changes, including splenomegaly, hepatomegaly, or granulomatous disease. These results suggest that the 16MΔmucR vaccine is safe, elicits a strong protective immunity, and should be considered as a promising vaccine candidate for human use.

From sea to shining sea: making collaborative rural research work.

Rural researchers collaborate on many levels to collect and analyze data, develop research reports and disseminate findings. While this collaboration is critical, there is a dearth of literature about research team collaboration within all stages of the research process. The purpose of this article is to discuss the research experience of 10 rural researchers scattered across Canada who participated in the study, Health Research: Accessible, Applicable and Useable for Rural Communities and Practitioners. Using focused ethnography, one aim of this study was to discover how research is utilized in rural and remote settings. The necessity of establishing networks to collect and manage data, and jointly analyze 72 qualitative transcripts from different geographical sites led to innovations and unexpected lessons learned. The research design provided significant opportunities to mentor undergraduate, masters and doctoral nursing students and to enhance the development of newly graduated doctoral nurses. These opportunities are crucial in the development of new researchers and in creating ongoing interest in rural health research. In this article, we discuss how the research process evolved, the mentoring process used, the barriers identified related to collaboration across vast distances, and the strategies employed to enhance the study's trustworthiness. We also consider the advantages and challenges of using Elluminate, a web application, as an interactive forum for this qualitative health research.

The Brucella abortus S19 DeltavjbR live vaccine candidate is safer than S19 and confers protection against wild-type challenge in BALB/c mice when delivered in a sustained-release vehicle.

Brucellosis is an important zoonotic disease of nearly worldwide distribution. Despite the availability of live vaccine strains for bovine (S19, RB51) and small ruminants (Rev-1), these vaccines have several drawbacks, including residual virulence for animals and humans. Safe and efficacious immunization systems are therefore needed to overcome these disadvantages. A vjbR knockout was generated in the S19 vaccine and investigated for its potential use as an improved vaccine candidate. Vaccination with a sustained-release vehicle to enhance vaccination efficacy was evaluated utilizing the live S19 DeltavjbR::Kan in encapsulated alginate microspheres containing a nonimmunogenic eggshell precursor protein of the parasite Fasciola hepatica (vitelline protein B). BALB/c mice were immunized intraperitoneally with either encapsulated or nonencapsulated S19 DeltavjbR::Kan at a dose of 1 x 10(5) CFU per animal to evaluate immunogenicity, safety, and protective efficacy. Humoral responses postvaccination indicate that the vaccine candidate was able to elicit an anti-Brucella-specific immunoglobulin G response even when the vaccine was administered in an encapsulated format. The safety was revealed by the absence of splenomegaly in mice that were inoculated with the mutant. Finally, a single dose with the encapsulated mutant conferred higher levels of protection compared to the nonencapsulated vaccine. These results suggest that S19 DeltavjbR::Kan is safer than S19, induces protection in mice, and should be considered as a vaccine candidate when administered in a sustained-release manner.

Inhibition of nitric oxide release pre-slaughter increases post-mortem glycolysis and improves tenderness in ovine muscles.

The aim of this experiment was to determine the effect of inhibiting the release of nitric oxide (NO) pre-slaughter in lambs on post-slaughter muscle metabolism and meat quality. Exercise was used as a positive control as NO is known to be released in skeletal muscle during exercise. Forty Border Leicester×Merino lambs were assigned to the treatments L-NAME (NO synthase inhibitor) infusion (0mg/kg vs. 30mg/kg, 135min pre-slaughter) and exercise (none vs. 15min immediately pre-slaughter). The inhibition of NO release using L-NAME reduced Warner-Bratzler shear force (WBSF) in the longissimus thoracis et lumborum (LTL) after 3days of ageing, while the Semimembranosous (SM) was unaffected. Inhibition of NO release with L-NAME resulted in altered glucose metabolism as indicated by reduced plasma glucose pre-slaughter particularly in exercised lambs, reduced LTL and SM glycogen of non-exercised lambs post-slaughter and increased SM lactate in exercised lambs post-slaughter. In conclusion, inhibition of NO Synthase with L-NAME pre-slaughter increases post-mortem glycolysis and improves tenderness in the loin muscle.

Aerosol infection of BALB/c mice with Brucella melitensis and Brucella abortus and protective efficacy against aerosol challenge.

Brucellosis is a zoonotic disease with a worldwide distribution that can be transmitted via intentional or accidental aerosol exposure. In order to engineer superior vaccine strains against Brucella species for use in animals as well as in humans, the possibility of challenge infection via aerosol needs to be considered to properly evaluate vaccine efficacy. In this study, we assessed the use of an aerosol chamber to infect deep lung tissue of mice to elicit systemic infections with either Brucella abortus or B. melitensis at various doses. The results reveal that B. abortus causes a chronic infection of lung tissue in BALB/c mice and peripheral organs at low doses. In contrast, B. melitensis infection diminishes more rapidly, and higher infectious doses are required to obtain infection rates in animals similar to those of B. abortus. Whether this difference translates to severity of human infection remains to be elucidated. Despite these differences, unmarked deletion mutants BADeltaasp24 and BMDeltaasp24 consistently confer superior protection to mice against homologous and heterologous aerosol challenge infection and should be considered viable candidates as vaccine strains against brucellosis.

Evaluation of protection afforded by Brucella abortus and Brucella melitensis unmarked deletion mutants exhibiting different rates of clearance in BALB/c mice.

Research for novel Brucella vaccines has focused upon the development of live vaccine strains, which have proven more efficacious than killed or subunit vaccines. In an effort to develop improved vaccines, signature-tagged mutant banks were screened to identify mutants attenuated for survival. Mutants selected from these screens exhibited various degrees of attenuation characterized by the rate of clearance, ranging from a failure to grow in macrophages after 24 h of infection to a failure to persist in the mouse model beyond 8 weeks. Ideal vaccine candidates should be safe to the host, while evoking protective immunity. In the present work, we constructed unmarked deletion mutants of three gene candidates, manBA, virB2, and asp24, in both Brucella abortus and Brucella melitensis. The Deltaasp24 mutants, which persist for extended periods in vivo, are superior to current vaccine strains and to other deletion strains tested in the mouse model against homologous challenge infection after 12, 16, and 20 weeks postvaccination. The Deltaasp24 mutants also display superior protection compared to DeltamanBA and DeltavirB2 mutants against heterologous challenge in mice. From this study, a direct association between protection against infection and cytokine response was not apparent between all vaccine groups and, therefore, correlates of protective immunity will need to be considered further. A distinct correlation between persistence of the vaccine strain and protection against infection was corroborated.

Inhibition of endogenous nitric oxide production influences ovine hindlimb metabolism independently of insulin concentrations.

The hindlimb arteriovenous difference (AVD) model was used to determine whether 30 mg/ kg of the nitric oxide synthase (NOS) inhibitor L-NGnitroarginine methyl ester (hydrochloride; L-NAME) inhibited ovine NO synthesis and influenced muscle metabolism. Eight Border Leicester x Merino cross lambs (50 to 55 kg BW) were infused with saline (control) or saline containing L-NAME via an indwelling jugular vein catheter in a balanced randomized crossover design with 3 d between treatments. The abdominal aorta and deep femoral vein were catheterized for assessment of AVD of hind limb metabolism. Arterial hematocrit and insulin concentration and both arterial and venous concentrations of nitrate/nitrite (NOx), glucose, lactate, NEFA, and urea were determined. Infusion of L-NAME decreased arterial NOx concentrations (P = 0.049), indicating inhibition of systemic NO synthesis. Treatment had no effect on arterial (3.5 vs. 3.6 +/- 0.19 mmol/L for control and L-NAME lambs, respectively; P = 0.39) or venous (3.3 vs. 3.4 +/- 0.16 mmol/L, P = 0.55) plasma glucose concentrations or on glucose AVD (0.19 vs. 0.27 +/- 0.065 mmol/L, P = 0.20). There was an interaction (P = 0.038) between time and treatment, such that L-NAME initially increased the AVD of glucose (up to 180 m) divergent from control lambs. The response was then decreased before a possible inflection beyond 240 min. Infusion of L-NAME increased hindlimb venous NEFA (222 vs. 272 +/- 13.2 micromol/L, P = 0.007) and NEFA AVD (79.4 vs. -13.3 +/- 31.5 micromol/L, P = 0.018). These metabolic changes were independent of plasma insulin concentrations, which were not affected by L-NAME infusion (25.3 vs. 27.8 +/- 3.62 mU/L, P = 0.85). The increase in hindlimb lipolysis after L-NAME infusion does not seem to be due to increased lipolysis of plasma triacylglycerol because circulating arterial (155 vs. 142 +/- 20.8 micromol/L, P = 0.58), venous (154 vs. 140 +/- 20.5 micromol/L, P = 0.50), and AVD (1.0 vs. 2.9 +/- 3.17 micromol/L, P = 0.38) triacylglycerol concentrations were unaffected by L-NAME infusion. In conclusion, these data indicate that infusion of 30 mg of L-NAME/kg inhibits NO synthesis, which in turn influences fat and carbohydrate metabolism in the ovine hindlimb independently of plasma insulin concentrations.

The York review--a systematic review of public water fluoridation: a commentary.

Following the election of the British government in May 1997, a policy document outlining proposals to improve the health of the nation was published. This document placed a major emphasis on reducing inequalities in health and recognised the continuing poor state of oral health in deprived communities. However, whilst acknowledging the benefits of water fluoridation as a caries preventive measure, the Department of Health suggested that most of the research had been carried out some years ago and furthermore, recognised that strong views were held both for and against fluoridation.

Visual and non-visual control of landing movements in humans.

1. The role of vision in controlling leg muscle activation in landing from a drop was investigated. Subjects (n = 8) performed 10 drops from four heights (0.2, 0.4, 0.6 and 0.8 m) with and without vision. Drop height was maintained constant throughout each block of trials to allow adaptation. The aim of the study was to assess the extent to which proprioceptive and vestibular information could substitute for the lack of vision in adapting landing movements to different heights. 2. At the final stages of the movement, subjects experienced similar peak centre of body mass (CM) displacements and joint rotations, regardless of the availability of vision. This implies that subjects were able to adapt the control of landing to different heights. The amplitude and timing of electromyographic signals from the leg muscles scaled to drop height in a similar fashion with and without vision. 3. However, variables measured throughout the execution of the movement indicated important differences. Without vision, landings were characterised by 10 % larger ground reaction forces, 10 % smaller knee joint rotations, different time lags between peak joint rotations, and more variable ground reaction forces and times to peak CM displacement. 4. We conclude that non-visual sensory information (a) could not fully compensate for the lack of continuous visual feedback and (b) this non-visual information was used to reorganise the motor output. These results suggest that vision is important for the very accurate timing of muscle activity onset and the kinematics of landing.

Both CD45R(low) and CD45R(high) "revertant" CD4 memory T cells provide help for memory B cells.

During a primary response to thymus dependent antigens, B cells undergo a number of qualitative changes to become memory B cells - processes that require co-stimulatory signals and cytokine help from CD4 T cells. The question of whether distinct, antigen-experienced memory CD4 T cells are subsequently needed to program memory B cells into antibody synthesis has not been clearly resolved. Using an adoptive transfer model in which memory but not naive B cells were stimulated, we evaluated CD4 T cell help using lymphocytes obtained from primed or unprimed thymectomized donors and expressing a naive (CD45R(high)) or a memory (CD45R(low)) phenotype. Memory B cells, most of which were committed to the IgG1 (Th2) subclass, could be stimulated to produce antibody using help transferred by the CD45R(high) naive subset of unprimed donors (slow onset of response), the CD45R(low) subset of 7 day primed donors (large, rapid antibody response) or by both the CD45R(low) and the CD45R(high) "revertant" subsets of 6 month primed donors. We found that antigen primed CD45R(low) CD4 T cells reverted (defaulted) with time to a CD45R(high) resting state, a change that was prevented by persisting antigen. The evidence suggests that CD4 memory T cells are partitioned into two different functional states (CD45R(high) and CD45R(low)) and that these determine the characteristics of the memory B cell response in terms of speed, size and longevity.