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Despite massive sequencing efforts, understanding the difference between human pathogenic and benign variants remains a challenge. Computational variant effect predictors (VEPs) have emerged as essential tools for assessing the impact of genetic variants, although their performance varies. Initially, sequence-based methods dominated the field, but recent advances, particularly in protein structure prediction technologies like AlphaFold, have led to an increased utilization of structural information by VEPs aimed at scoring human missense variants. This review highlights the progress in integrating structural information into VEPs, showcasing novel models such as AlphaMissense, PrimateAI-3D, and CPT-1 that demonstrate improved variant evaluation. Structural data offers more interpretability, especially for non-loss-of-function variants, and provides insights into complex variant interactions in vivo. As the field advances, utilizing biomolecular complex structures will be pivotal for future VEP development, with recent breakthroughs in protein-ligand and protein-nucleic acid complex prediction offering new avenues., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Joseph Marsh reports financial support was provided by UK Research and Innovation Medical Research Council. Sarah Teichmann reports a relationship with Sanofi that includes: board membership. Sarah Teichmann reports a relationship with GlaxoSmithKline Inc that includes: board membership and employment. Sarah Teichmann reports a relationship with Foresite Labs that includes: board membership. Sarah Teichmann reports a relationship with QIAGEN GmbH that includes: board membership. Sarah Teichmann reports a relationship with Transition Bio, Inc. that includes: equity or stocks. Sarah Teichmann reports a relationship with Ensocell that includes:. Sarah Teichmann reports a relationship with 10x Genomics, Inc. that includes: board membership. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Motivated by the unexplained variation in the performance of some vaccines across different settings, we extend previous theoretical work to consider the potential impact of incomplete case ascertainment on measures of vaccine efficacy (VE), which is more likely in subclinical or clinically unimportant infections, such as rotavirus gastroenteritis., Methods: By simulating the measurement of VE under outbreak conditions using a discrete time stochastic SIR model, we compare three commonly used measures, VE Risk , VE Rate , and VE Hazard , calculated respectively based on risk ratio, rate ratio and hazard ratio of disease. We investigate how these measures are influenced by factors such as biological activity, action mechanism of vaccine, proportion of cases ascertained, and underlying force of infection., Results: Under plausibly low levels of ascertainment, the group with the most infections, and therefore the most missed cases, has the most falsely inflated denominator, producing similar rates in the control and intervention groups. As a result, VE Rate and VE Hazard will underestimate the true VE compared to high case ascertainment scenarios. Furthermore, the extent of underestimation is greater for leaky vaccine models with lower biological protective effects and under conditions which are conducive to high transmission., Conclusions: This study demonstrates that a biologically active vaccine may produce a low measured VE under a range of epidemiological, vaccine-related and logistical conditions. Low case ascertainment may partly explain the observed heterogeneity in the performance of rotavirus vaccine across different settings, and should be considered in the design and interpretation of future field trials., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Most proteins assemble into complexes, which are involved in almost all cellular processes. Thus it is crucial for cell viability that mechanisms for correct assembly exist. The timing of assembly plays a key role in determining the fate of the protein: if the protein is allowed to diffuse into the crowded cellular milieu, it runs the risk of forming non-specific interactions, potentially leading to aggregation or other deleterious outcomes. It is therefore expected that strong regulatory mechanisms should exist to ensure efficient assembly. In this review we discuss the cotranslational assembly of protein complexes and discuss how it occurs, ways in which it is regulated, potential disadvantages of cotranslational interactions between proteins and the implications for the inheritance of dominant-negative genetic disorders., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Protein flexibility spans a broad spectrum, from highly stable folded to intrinsically disordered states. In this review, we discuss how various techniques, including X-ray crystallography, nuclear magnetic resonance spectroscopy and ensemble-modeling strategies employing various experimental measurements, have enabled detailed structural and dynamic characterizations of proteins in their free and bound states. This has revealed a variety of possible binding scenarios in which flexibility can either decrease or increase upon binding. Furthermore, dynamic free-state ensembles have repeatedly been observed to contain transiently formed conformations that partially or completely resemble bound states. These results demonstrate an intimate connection between protein flexibility and protein interactions and illustrate the huge diversity of structure and dynamics in both free proteins and protein complexes., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The mechanism of elite control of HIV-1 replication is not fully understood. While immunosuppression due to rituximab based chemotherapy has been associated with increased replication of HBV, CMV, and HIV-1, control of replication-competent HIV-1 was maintained in an elite controller/suppressor treated with a regimen that included vincristine, cyclophosphamide, prednisone, four rounds of plasmapheresis and ten cycles of rituximab. The data suggests that de-novo antibody responses do not play a significant role in the control of viral replication in these patients., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Beginning at hatching, male Cornell K strain single comb white leghorn chickens were fed a basal diet, with or without vitamin E (100 IU/kg) and/or selenium (Se, 0.2 ppm). After 3 weeks of treatment, animals fed either the Se-deficient or basal diet had significantly reduced plasma Se-dependent glutathione peroxidase activities when compared to those fed a vitamin E and Se-supplemented diet. Similarly, animals fed the vitamin E-deficient or basal diet had significantly reduced plasma alpha-tocopherol levels. The effect of these treatments on plasma concentrations of thyroid hormones (T(3)/T(4)), growth hormone (GH), and thymic hormone (thymulin) was determined using radioimmunoassay and ELISA. A deficiency in Se, but not in vitamin E, resulted in an increase in plasma T(4) concentrations while plasma T(3) concentrations were decreased. Plasma GH levels showed some fluctuation as a result of the dietary treatments but there was no significant correlation between plasma GH levels and any of the other variables. A significant decrease in plasma thymulin levels was observed in Se-deficient birds compared to those receiving adequate Se in the diet. A vitamin E deficiency had no measurable effect on plasma thymulin levels. From these studies, we conclude that plasma thymulin concentrations directly correlate with plasma T(3) concentrations which are negatively affected by a Se deficiency.

Previous work has shown that in vitro thymulin treatments have the ability to enhance natural killer (NK) cell cytotoxicity. The purpose of the experiments presented here was to examine the in vivo effects of thymulin on avian NK cell activity in response to a viral infection. Five and a half-week-old K-strain chickens infected with avian infectious bronchitis virus (IBV) served as the model for these experiments. Daily thymulin injections began at varying time points prior to or post-infection. The controls received daily injections of the ZnCl(2)-containing carboxymethyl-cellulose (CMC) diluent. A 51Cr-cytolytic release assay was used to determine the activity of the NK cells harvested via lung lavage from the respiratory tracts of infected chickens. The results of these experiments showed that in vivo thymulin treatments enhance NK cytotoxicity. The greatest enhancement of NK cytotoxicity was observed at 10 days post-infection in those chickens that began receiving thymulin after infection. These results suggest that thymulin may not only have a role in enhancing immunosurveillance but also in enhancing the response of the innate immune system following infection. Dose-response experiments found that the 50 ng/100 g body weight (Bwt) dose significantly depressed the cytolytic activity of the NK cells in comparison to either the 10 ng/100 g Bwt dose or the control., (Copyright 2002 Elsevier Science B.V.)

Preincubation with either thymulin or IFN-gamma can enhance NK activity. In addition, overnight in vitro pre-treatment with thymulin and IFN-gamma increases NK activity further than either treatment alone. It has been hypothesized that thymulin increases the responsiveness of immune cells to IFN-gamma by either increasing the expression of IFN-gammaR or by increasing the production and/or secretion of IFN-gamma. The effects of thymulin on IFN-gamma production and secretion were examined in this study. While an overnight incubation with the polyclonal activator Con A increased the number of cells positive for intracellular IFN-gamma, a similar incubation with thymulin produced no change in the percentages of cells labeling positive for intracellular IFN-gamma when compared to the media control cells. In addition, IFN-gamma was not secreted by splenocytes following an overnight incubation with thymulin, but increased secretion was induced by Con A stimulation. Taken together, these results suggest that thymulin does not increase IFN-gamma production or induce IFN-gamma secretion by avian splenocytes.

The effect of in vivo and in vitro thymulin treatments on macrophage responsiveness to interferon-gamma was evaluated in chickens. Seven-week-old chickens were treated with 0, 1, 10, or 100ng thymulin per 100g body weight. Abdominal exudate cells (AEC), a source of macrophages, were harvested and cultured in the presence of graded levels of recombinant chicken interferon-gamma (ChIFN-gamma). Responsiveness to ChIFN-gamma was determined by measuring the induction of nitric oxide production. One and 2-day thymulin treatment at 10 and 100ng per 100g body weight doses significantly increased responsiveness to ChIFN-gamma while 1ng per 100g body weight had no effect. Other experiments compared the effect of thymulin treatments in Cornell K strain chickens, having normal serum thymulin levels with sex-linked dwarf (SLD) chickens which are deficient in serum thymulin. The dose of thymulin treatment required to significantly increase responsiveness to ChIFN-gamma differed between strains. Finally, the effect of direct in vitro thymulin treatments on macrophage responsiveness to ChIFN-gamma was evaluated. There were no significant increases in responsiveness to ChIFN-gamma between treatment groups within the macrophage cell line, HD-11, when cultured in the presence of 0-200pg thymulin/ml. These data suggest that the effect of thymulin on AEC responsiveness to ChIFN-gamma is indirectly mediated.

The effects of triiodothyronine (T3), thymulin, and recombinant chicken interferon-y (ChIFN-gamma) on natural killer (NK) cell cytotoxicity was investigated using the euthyroid control K and the T3-deficient sex-linked dwarf (SLD) chicken strains. Factorial design experiments were used to investigate the effects of T3 treatments where animals of both strains received either 0 or 0.1 ppm T3 supplementation to the standard chick starter diet. The ChIFN-gamma treatments were administered in vitro by incubation with effector cells overnight prior to the addition of the RP9 lymphoblastoma target cell line. All cytotoxicity assays were run at 50:1 and 25:1 effector/target (E/T) ratios. Treatments were begun at hatching and continued through 7 weeks. NK cells for these assays were enriched by separation of splenocytes over ficoll. Splenocyte preparations from untreated K strain consistently had significantly higher NK-mediated cytolysis than did samples from the untreated SLD at both E/T ratios. T3 treatment alone had no effect on NK activity in cell preparations from the K strain but did significantly enhance that activity in the T3-deficient SLD whereas IFN treatment alone enhanced NK activity in both strains. The combined T3 and IFN treatments resulted in a greater enhancement of NK cytolytic activity in both strains than any separate treatment and resulted in an elimination of differences in NK cell responsiveness between the K and SLD strains. Similar results were obtained when NK cell cultures were incubated in vitro with thymulin prior to assessing cytotoxicity. In vitro thymulin treatments alone significantly enhanced cytolytic activity for NK cells for both K and SLD strains. The greatest effect of in vitro thymulin exposure was to increase the responsiveness to NK cells to ChIFN-gamma stimulation.

The ability of thymulin to directly enhance NK cell-mediated cytotoxicity was examined. Specific cell population depletions were done in K and SLD chicken splenocyte preparations using anti-CD3, CD4, and CD8 monoclonal antibodies and secondary complement-fixing polyclonal antibodies. The remaining cells were incubated overnight with in vitro treatments of thymulin and IFN-gamma, either separately or together, followed by an assay for cytotoxicity. Although the control K-strain had higher overall NK cell-mediated cytotoxicity than the thymulin-deficient SLD-strain, the following trends were seen in both strains. Thymulin continued to enhance NK activity following CD4 or CD3 cell depletion, but not after CD8 or CD8 and CD4 cell depletion. Since avian NK cells express CD8 alpha, but not CD3 or CD4 on their surface, these results suggest that the ability of in vitro thymulin treatments to enhance NK activity is not mediated by T-cells but may be due to direct effects on NK cells.

The effect of thymulin on IL-2 receptor (IL-2R) expression by avian splenocytes was examined in the functionally hypothyroid sex-linked dwarf (SLD) and in normal euthyroid K strain chickens. Daily thymulin injections of 0, 0.05 and 5.0 ng/100 g body weight were given from hatching until 4 weeks of age. ConA-treated and non-stimulated splenocytes from these animals were analyzed by flow cytometry for their expression of IL-2Ralpha, CD4 and CD8 cell surface molecules. ConA activation increased the number of IL-2R+ cells within K strain more than in the SLD. Thymulin treatment increased the number of IL-2R+ cells in the SLD but had the opposite effect in K strain chickens. Mitogen activation or thymulin treatment had little effect on the IL-2R density within small cell populations. In contrast, mitogen activation increased the density of IL-2R on larger cell populations in both K and SLD. IL-2R densities on non-stimulated larger cells decreased in the SLD after thymulin exposure. Thymulin treatment produced no effect on the mean IL-2R densities for large activated cells. ConA stimulation increased the number of CD4+ cells in both strains. The density of CD4 expression was modulated by both mitogen activation and thymulin treatment. ConA stimulation produced an increase in the number of CD8+ cells. The SLD had fewer CD8+ cells than did the K strain and thymulin treatment had little effect on this population in either strain. Mitogen stimulation increased the density of CD8 on CD8+ cells but again thymulin treatment had little effect. These results suggest that thymulin can modulate IL-2R expression on splenocytes and that this effect may be dependent upon the thyroidal status of the animal. Further, these data suggest that thymulin has a differential effect on the CD4 and CD8 T-cell subpopulations.

Cornell K strain chickens received a diet supplemented with 0, 0.1 and 1.0 ppm T3 from the day of hatching. At 28 days of age, splenocyte suspensions were prepared and analyzed by flow cytometry for interleukin-2 receptor (IL-2R) and CD3 expression. The low T3 dose increased the percentage of resting small cells expressing IL-2R while the mean fluorescence for this marker was enhanced only after mitogenic activation. This treatment did not alter the number of larger cells positive for IL-2R but did increase their mean fluorescence following mitogenic activation. The high T3 dose depressed the numbers of cells positive for IL-2R and their mean fluorescence amongst all splenocyte preparations. Both levels of T3 enhanced the numbers of CD3-positive cells in all cell preparations. These results suggest that the IL-2R expression can be modulated by in vivo T3 supplementation and that these correlate with the previously demonstrated changes in IL-2-like activity. The regulation of IL-2R expression provides one mechanism through which thyroid status may regulate immune function.

The effect of thyroxine (T4) and recombinant (rcGH) or purified pituitary-derived (pcGH) chicken growth hormone on the development of spontaneous autoimmune thyroiditis (SAT) was examined in the Obese strain (OS) chicken. Day-old OS chicks were randomly assigned to a control or 1.0 ppm T4 supplemented diet and a vehicle or 500 micrograms rcGH/kg BW daily injection, using a 2 x 2 factorial design. At 4 weeks, sera were analyzed for anti-thyroglobulin autoantibody (TgAAb) using a kinetics-based ELISA. Leucocytic infiltration of the thyroid was assessed using computer-based video imaging techniques. A close correlation between TgAAb and thyroid infiltration was seen with both being decreased (p < 0.05) by the T4/rcGH treatment. Neither the T4 or rcGH alone produced this effect and the rcGH treatment significantly elevated TgAAb. In a second experiment, all but the control group received 1.0 ppm T4 supplementation and two of the T4-treated groups received either 50 or 200 micrograms pcGH/kg BW by daily injection. As before, T4/pcGH significantly reduced TgAAb and thyroid infiltration. T4 alone produced no significant effects. These data support the conclusion that the combined treatment of T4 and cGH exert an immunomodulatory effect within a strain that is predisposed to autoimmune thyroiditis while GH treatment alone exacerbated the condition. These results also show that video imaging techniques can be used to evaluate the extent of histopathology present within the OS thyroid.

One-day-old chickens were treated with varying levels of triiodothyronine (T3) added to the diet. At 28 days of age, the IL-2-like activity in the splenocyte culture supernatants were assessed. The lowest dose of T3 (0.1 ppm) enhanced IL-2-like activity while the highest dose (1.0 ppm) was significantly suppressive. The intermediate dose elicited varying effects. Recombinant chicken growth hormone (rcGH) was added to some cultures 24 h prior to IL-2 assay. In vitro rcGH significantly depressed the IL-2-like activity of splenocytes from animals given the low T3 diet. The addition of varying concentrations of T3 in vitro to splenocytes from non-T3-supplemented chickens had no effect on the IL-2-like activity. These results indicate that in vivo supplementation of low dietary T3 but not in vitro T3 is effective in enhancing avian IL-2-like activity. The addition of rcGH in vitro can modify this response.

The effect of hypophysectomy and recombinant growth hormone (rcGH) treatment on the growth and development of the immune system was investigated in young chickens. Flow cytometric analysis of cell surface markers revealed no changes in the proportion of thymocytes expressing CT-1a, CD4, and/or CD8 among any of the treatment groups. In contrast, the proportion of both single positive CD4 and CD8 peripheral blood lymphocytes (PBL) was altered in hypox birds treated with rcGH compared to the vehicle-treated group. Specifically, rcGH treatment produced a decrease in the proportion of CD8+ cells and an increase in the percentage of CD4+ PBL. There was little change in the labeling intensity of PBL or thymocytes associated with any treatment; however, double positive (CD4+CD8+) thymocytes from hypophysectomized chicks that were not given rcGH had increased fluorescence relative to rcGH supplemented hypox chicks. As expected, hypophysectomy reduced body, skeletal, and thymic growth. Treatment of hypox chicks with rcGH enhanced body weight while thymic weights were somewhat increased. Skeletal growth was not significantly altered by rcGH. Bursal growth appeared refractory to either treatment. These studies support the conclusion that growth hormone influences thymic growth and the maturation of thymus-derived lymphocytes. These results also demonstrate a biological activity for chicken growth hormone derived through recombinant technology.

The effects of the in vitro exposure of avian bone marrow (BM) cells and thymocytes to synthetic thymulin were studied. Two T-cell differentiation markers, PNA binding site and CT-1a expression, were used to examine cell maturation. Enhanced PNA binding to both BM cells and thymocytes resulted following an in vitro thymulin exposure but cell proliferation was not affected. Scatchard analysis supported the conclusion that PNA binding affinity was significantly increased and thus responsible for the observed increase in PNA binding. Flow cytometric analysis suggested that the induced PNA+ thymocyte population may be a different population from the one exhibiting enhanced CT-1a expression following thymulin exposure. Taken together, the observations suggest that cells can express their further differentiation states without undergoing proliferation following in vitro thymulin stimulation.

The kinetics of serum autoantibody production against thyroglobulin (Tg) was examined in two strains of chicken using an enzyme-linked immunosorbant assay (ELISA). Both strains are homozygous for the B13 haplotype. The OS strain develops spontaneous autoimmune thyroiditis at several weeks of age while the Sp. C strain, which serves as the control for the OS strain, has virtually undetectable autoantibody levels as determined by hemagglutination assay (HA). Serum autoantibody levels in both strains were monitored bi-weekly from 6 through 14 weeks of age post-hatching, using both the ELISA and HA techniques. With the more sensitive ELISA, absolute serum autoantibody concentrations were determined and both the Sp. C and OS strains were found to have readily detectable serum autoantibodies against Tg; however, the OS did have significantly higher autoantibody levels than the Sp. C strain. In the latter strain, autoantibodies increased significantly with age while the pattern was somewhat reversed in the OS strain. The ELISA revealed that the decline of Tg autoantibodies with age in the OS strain was restricted primarily to males, with females maintaining constant levels of autoantibodies. In contrast, the HA detected only the differences in autoantibody levels between the OS and Sp. C strains.

The response of lymphocytes to concanavalin A (Con A) was examined in the functionally hypothyroid SLD strain and the normal K strain chickens which were fed diets with or without T3 supplementation (0.1, 0.5 and 1.0 ppm) since the time of hatch. Peripheral blood lymphocytes (PBL) from 3 and 12 week old male and female chickens were incubated with Con A for 60 h. Mitogenic responsiveness was assessed by measuring the uptake of 3H-thymidine during the last 24 h of incubation. There was no difference in the mitogen response between male and female chickens. The mitogen responsiveness of PBL from the K strain tended to be greater than that from the SLD strain at both ages. The lowest dose of T3 (0.1 ppm) had no effect on the mitogen response of 3-week-old K strain chicks but caused an increase in mitogen response in 3-week-old SLD and in 12-week-old birds of both strains. Supplementation with 0.5 and 1.0 ppm T3 tended to decrease mitogen responsiveness in the K and SLD strain at both ages. The effect of treatment on thymus weights, bursa weights, and lymphocyte concentrations of the blood was also assessed.

The effects of dietary thyroxine (T4) supplementation for specific periods on the early development of the primary lymphoid organs and spontaneous autoimmune thyroiditis (SAT) was examined in the Obese (OS) strain of chicken. Effects of the treatments on concentrations of serum growth hormone (GH) and testosterone were also determined. All treatment groups were examined at 6 weeks. T4 supplementation did not affect serum testosterone or GH concentrations. However T4 given for the first three weeks resulted in significantly increased bursa weights, no change in thymic weights, significantly decreased lymphoid infiltration of the thyroid and reduced thyroglobulin autoantibody levels (TgAAb). T4 supplementation for the full six weeks resulted in no change in bursal weight, significantly increased thymic weight, significantly decreased lymphoid infiltration of the thyroid, and reduced TgAAb. These results suggest that the effects of T4 supplementation on SAT and immune development are dependent on the interval during which it is administered and that testosterone and GH probably do not mediate these effects.

The effect of dietary triiodothyronine (T3) supplementation (0, 0.1, 0.1, and 1.0 ppm of T3) on the mixed lymphocyte response (MLR) was examined in MHC-matched young Cornell K and sex-linked dwarf (SLD) strain cockerels at ages 6, 9, and 12 weeks. At all ages, MLR in SLD strain cockerels was significantly lower than in the K strain. Supplementation of 6-week-old cockerels with 0.01 and 0.1 ppm of T3 tended to decrease MLR in both strains, whereas the highest dose of T3 had the opposite effect in the K strain and no effect in the SLD strain compared to the control. No significant effects of T3 on MLR were observed in 9-week-old cockerels. A significant main treatment effect of T3 on MLR was observed in 12-week-old cockerels. At this age dietary T3 decreased MLR in both strains. These results show that allo-aggression, a functional parameter of cell-mediated immunity, can be affected by non-MHC controlled strain differences and by the iodothyronine state of these strains.

The humoral immune response was examined in two dwarf and one control strain of Single Comb White Leghorn chicks. Circulating antibody levels in response to immunization with varying concentrations of sheep erythrocytes were determined following primary immunization and again following a secondary antigen challenge. The males of the sex-linked dwarf strain produced significantly less antibody to lower antigen dosages in both the primary and secondary response but as antigen dose was increased the humoral response was no longer depressed below that of the controls. The antibody response of females carrying the dw gene was not significantly impaired over the entire antigen dose range nor was that of either sex of the autosomal dwarf strain. Similar results were obtained when the numbers of splenic plaque-forming cells (PFC's) were examined. However, in this assay both the males and females of the sex-linked dwarf strain demonstrated significantly impaired plaque-forming activity. No differences were found between the control and autosomal dwarf strains in their ability to generate PFC's.

Two independent experiments were conducted to examine the ability of 1) the autosomal-dwarf (ADW) strain and 2) the sex-linked (SLD) strain chicken to make a Graft-versus-Host (GvH) response. In each experiment the GvH response of the dwarf strain was compared to the GvH response of a normal growing control strain, the Cornell K strain chicken. All 3 strains were homozygous B15/B15 at the major histocompatibility complex. GvH responsiveness of peripheral blood lymphocytes (PBL) from females of each strain was assessed at various intervals from 1.5 to 20 months of age using the chorio-allantoic membrane (CAM) assay. The GvH response in female chickens from the ADW strain was significantly higher than in K strain females after the birds had reached sexual maturity (after 5.5 months). The GvH response in females from the SLD strain was, however, significantly lower than in the K strain females throughout the experiment. All strains tended to have a biphasic GvH response. There was a significant increase in GvH responsiveness from 1.5 to 5.5 months of age in chicks from all strains. In the SLD and K strain chickens, this was followed by a drop in the GvH response until 8.5 months of age. In 16- to 20-month-old SLD and K strain hens, the ability to mount a GvH response returned to levels observed in younger (5.5 months) pullets. The GvH responsiveness of the ADW strain remained at a constant level from 5.5 to 12 months of age. However, a second peak in GvH responsiveness was observed in 16-month-old ADW strain hens. Strain differences in GvH responsiveness may be due to the known hormonal abnormalities in the dwarf strains. The suitability of these dwarf strains for the study of endocrine-immune interrelationships is discussed.