[The action of laser radiation on thymic hormone production]. / Deistvie lazernogo izlucheniia na vyrabotku gormonov timusa.

Irradiation of the epithelial cells from human thymus (cell line HTSC) by arsenid-gallium laser (0.89 nm, 1500 Hz) induces an enhancement of thymic hormone production. The concentration of alpha-1-thymosin was substantially increased on the days 1 and 5 in culture after irradiation. The increase of thymulin level in cultural supernatants was less pronounced and displayed after irradiation during 3-4 minutes. Local laser irradiation of thymus region of rats (5 minutes, 10 times) induce the increase of serum concentration of alpha-1-thymosin and the decrease of serum level of thymulin 2 days after irradiation.

Hormonas tímicas como mediadoras de la integración inmunogonadotropa / Thymic hormones as mediators of the inmunogonadotroph integration

Existe significativa evidencia sobre la existencia de un eje timo-hipofiso-gonadal. En razón de que estudios previos de los autores habían demostrado que la Hormona Homeostática Tímica, un dímero de histonas H2A y H2B, posee múltiples efectos in vivo sobre la secreción de hormonas hipofisarias, resultó de interés evaluar el efecto in vitro de distintas preparaciones tímicas y proteínas nucleares relacionadas, sobre la liberación de prolactina (Prl), hormona foliculoestimulante (FSH) y hormona luteinizante (LH). Células hipofisarias frescas de ratas hembras se dispersaron con colagenasa y se empaquetaron en una columna de Biogel P-2 mantenida a 37oC. Las células se perifundieron continuamente con medios EBSS, o,5 por ciento de BSA, 1 por ciento de ácido ascórbico y 50 IU de aprotinina/ml (medio de perifusión, MP). Las sustancias a ser testeadas (estímulos) se disolvieron en MP, perifundiéndose en un volumen de 1,5 ml por estímulo a través del circuito de perifusión, al final del cual se recogieron fracciones de 1 ml. Las hormonas liberadas se dosaron por radioinmunoensayo. La viabilidad de las células dispersas osciló entre 84 y 96 porciento. Distintas diluciones de extractos de eminencia media de rata generaron, para cada hormona, una respuesta estimulatoria dosis-dependiente. En general, tanto las preparaciones de histona H2A como las de nucleohistona (ambas a una concentración de 500 µg/ml) indujeron picos secretorios significativos de LH, FSH y Prl, siendo los más elevados los correspondientes a Prl. Asimismo, la hormona tímica timulina y sobrenadantes provenientes de cultivo de células epiteliales tímicas de rata y ratón, pero no la timosina fracción ÷ o el péptido tímico MB-35, resultaron estimulatorios. Los resultados del presente trabajo sugieren que ciertos productos tímicos podrían participar en la integración inmuno-gonadotropa, actuando como señales hipofisotropas

Hormonas tímicas como mediadoras de la integración inmunogonadotropa / Thymic hormones as mediators of the inmunogonadotroph integration

Existe significativa evidencia sobre la existencia de un eje timo-hipofiso-gonadal. En razón de que estudios previos de los autores habían demostrado que la Hormona Homeostática Tímica, un dímero de histonas H2A y H2B, posee múltiples efectos in vivo sobre la secreción de hormonas hipofisarias, resultó de interés evaluar el efecto in vitro de distintas preparaciones tímicas y proteínas nucleares relacionadas, sobre la liberación de prolactina (Prl), hormona foliculoestimulante (FSH) y hormona luteinizante (LH). Células hipofisarias frescas de ratas hembras se dispersaron con colagenasa y se empaquetaron en una columna de Biogel P-2 mantenida a 37oC. Las células se perifundieron continuamente con medios EBSS, o,5 por ciento de BSA, 1 por ciento de ácido ascórbico y 50 IU de aprotinina/ml (medio de perifusión, MP). Las sustancias a ser testeadas (estímulos) se disolvieron en MP, perifundiéndose en un volumen de 1,5 ml por estímulo a través del circuito de perifusión, al final del cual se recogieron fracciones de 1 ml. Las hormonas liberadas se dosaron por radioinmunoensayo. La viabilidad de las células dispersas osciló entre 84 y 96 porciento. Distintas diluciones de extractos de eminencia media de rata generaron, para cada hormona, una respuesta estimulatoria dosis-dependiente. En general, tanto las preparaciones de histona H2A como las de nucleohistona (ambas a una concentración de 500 Ag/ml) indujeron picos secretorios significativos de LH, FSH y Prl, siendo los más elevados los correspondientes a Prl. Asimismo, la hormona tímica timulina y sobrenadantes provenientes de cultivo de células epiteliales tímicas de rata y ratón, pero no la timosina fracción ¸ o el péptido tímico MB-35, resultaron estimulatorios. Los resultados del presente trabajo sugieren que ciertos productos tímicos podrían participar en la integración inmuno-gonadotropa, actuando como señales hipofisotropas (AU)

Suppressin: an endogenous negative regulator of immune cell activation.

We have recently identified a new suppressor molecule we named suppressin (SPN) that has all the characteristics of a global negative regulator of the immune system. SPN is a unique 63-kD monomeric polypeptide with a pI of 8.1 that is produced and secreted under basal conditions by murine splenocytes, human peripheral mononuclear cells, and hormone-secreting pituitary cells. The biological actions of SPN in vitro include the inhibition of mitogen-induced proliferation and immunoglobulin synthesis of lymphocytes and the suppression of interleukin-2-dependent CTLL-2 cell proliferation. In addition, SPN enhances natural killer cell activity by eliciting interferon-alpha and -beta synthesis and secretion. SPN effects are reversible, nontoxic, and require the continuous presence of exogenous SPN. T lymphocytes stimulated with concanavalin A or phytohemagglutinin are more sensitive to SPN (90% inhibition) than are lipopolysaccharide-stimulated B cells (60% inhibition). SPN arrests lymphocytes in the G0/G1 phase of the cell cycle after reduction of their RNA, protein and DNA synthesis, suggesting that SPN inhibits the processes required for G0 transition to G1. SPN is found intracellularly in all unstimulated lymphocyte subsets, monocytes, and in phytohemagglutinin-activated T lymphocytes immunopositive for the low affinity interleukin-2 receptor. These results suggest that SPN may be a major negative regulator of cell proliferation in the immune system. All SPN-producing cell types are also sensitive to SPN. Collectively, the results of these experiments provide the foundations for a model in which SPN regulates lymphocyte proliferation in an autocrine and/or paracrine manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Identification of suppressin-producing cells in the rat pituitary.

Suppressin (SPN) is a novel polypeptide that is synthesized and secreted by normal rat pituitary cells and a rat pituitary tumor cell line, GH3. Specifically, SPN is a negative regulator of growth that inhibits lymphoid and neuroendocrine cell proliferation. The objective of the present study was to identify the cells in the normal rat pituitary that produce SPN. A double immunofluorescence technique, using antibodies to SPN in conjunction with antibodies to the six major adenohypophyseal hormones, was used to colocalize SPN and a specific hormone in a single dispersed pituitary cell. The results of these experiments showed that, on the average, 42% of the cells in the pituitary produce SPN. Suppressin production in the pituitary was restricted to the adenohypophysis. The SPN-producing population in the pituitary was composed of somatotrophs, lactotrophs, corticotrophs, thyrotrophs, and mammosomatotrophs, while gonadotrophs did not produce SPN. Additionally, a PRL reverse hemolytic plaque assay was used to examine SPN production in lactotrophs. The results of these experiments showed that SPN production and the amount of PRL secreted covaried. Specifically, SPN production was observed primarily in non-PRL-secreting lactotrophs or in lactotrophs secreting a high amount of PRL. The results of these experiments suggest a potential regulatory relationship between the synthesis and secretion of SPN and PRL. In summary, this report provides the first identification of SPN-producing cells in the pituitary and shows that SPN production occurs primarily in somatotrophs and lactotrophs.

Stimulatory effect of thymic factor(s) on steroidogenesis in cultured rat granulosa cells.

Thymic cells from immature female rats were isolated and used for production of thymic cell culture conditioned medium (TCM). Granulosa cells were obtained from immature diethylstilbestrol (DES)-treated rats. TCM stimulated basal progesterone and estradiol secretion from the granulosa cells in a dose and time dependent manner. Maximal stimulation of progesterone production occurred at 48 hours of incubation, during which period TCM caused approximately 5 times more progesterone secretion than heart cell conditioned medium (HCM) or mock extract (ME). The maximum progesterone secretion by granulosa cells occurred when they were exposed to 48% TCM causing 7 times more progesterone secretion than controls. Under the same maximum stimulatory conditions, however, TCM only approximately doubled estradiol secretion compared to concentrations secreted in the presence of HCM or ME. Thus, the effect of TCM on progesterone secretion was more prominent than its effect on estradiol secretion. The stimulatory action of TCM was not mimicked by HCM, thymosin-alpha 1 or thymulin. Furthermore, the stimulatory action of TCM on steroidogenesis did not appear to be mediated by the cAMP system. The stimulatory factor(s) in TCM were heat, acid and acetone labile, but could not be sedimented by activated charcoal. Thus, the present study demonstrates that the secretory product(s) of thymic epithelial cells can stimulate steroidogenesis in cultured rat granulosa cells. Our data imply that thymic factor(s) may have a direct effect on ovarian function.

Histology of the normal thymus.

We present a review of the normal histology of the thymus, with special emphasis on the developmental, morphologic, and immunohistochemical aspects pertinent to the interpretation of thymic lesions in surgical pathology. Attention is drawn to normal variations in histology, embryonal vestiges and developmental defects, involutional and hyperplastic changes, tissue reactions to injury, and biopsy artifacts that may constitute a source of diagnostic problems.

Neuroendocrine-thymus interactions. I. In vitro modulation of thymic factor secretion by thyroid hormones.

Several in vivo experimental and clinical studies suggest that the production of thymic hormones, such as thymulin (Zn-FTS), is modulated by thyroid hormones. It was not determined in these studies, however whether such modulation is exerted directly on the thymic epithelial cells which synthesize and secrete thymic hormones. In order to discriminate between direct and indirect modulation, the effect of thyroid hormones on the in vitro production of thymulin by whole thymic organ culture, as detected by the rosette inhibition assay, has been investigated. Donors of thymuses were young 6N-propyl-2 thiouracil (PTU)-treated hypothyroid Balb/c mice and normal littermates. Thymuses from hypothyroid mice were shown to produce concentrations in vitro nearly undetectable of thymic hormone, when compared to thymuses from normal mice. The in vitro addition of triiodothyronine (T3) caused a complete recovery of the thymic hormone production by thymuses from hypothyroid mice and an increased synthesis even by normal thymuses over control values. The complete blockade of in vitro thymic hormone production with cycloheximide, which inhibits mRNA and protein synthesis but not thyroid hormone permissive actions, suggests that the T3 induced increment of thymic hormone level in the supernatant is due to de novo synthesis. Furthermore, the number of thymulin-producing cells, as detected by immunofluorescence using a specific antithymulin monoclonal antibody, which is quite low in thymuses from hypothyroid mice, is completely regained after in vitro incubation with T3. These findings support the idea that the modulation of thyroid hormones on thymic endocrine activity is directly exerted at thymic level.

Neuroendocrine control of thymic hormonal production. II. Stimulatory effects of endogenous opioids on thymulin production by cultured human and murine thymic epithelial cells.

Data have now accumulated to strongly demonstrate that several neuropeptides, including endogenous opioids, can have immunomodulatory functions. Most of the studies have so far focused on the direct action of these substances on lymphocytes. We decided to investigate whether thymic epithelial cells (TEC) - the major component of the thymic microenvironment - could also be modulated by endogenous opioids. Primary cultures of human and murine TEC were subjected to several opioids (alpha-beta- or gamma-endorphins, as well as met- or leuenkephalins) applied in concentrations ranging from 10(-6) to 10(-9) M. On the following days we measured the levels of thymulin (a chemically-defined thymic hormone known to stimulate some steps of T-cell differentiation) in the culture supernatants, as well as the numbers of thymulin containing cells, evaluated by immunofluorescence with an anti-thymulin monoclonal antibody. After treatment of TEC cultures with beta-endorphin or leu-enkephalin a significant increase in the levels of thymulin in the culture media was observed, paralleled by a rise in the percentage of thymulin containing cells. In addition, this stimulatory effect was dose-dependent. Preincubation of the opioids with the specific antibodies abrogated the opioid-induced stimulatory effect on TEC. Moreover, naloxone, an opioid receptor antagonist, blocked the effect of beta-endorphin on thymulin production, suggesting that the effect of this neuropeptide on epithelial cells was mediated by an opioid receptor. Importantly, no effect on thymulin production was observed with the other opioids used, whatever the dose. These results suggest that, at least in vitro, beta-endorphin and leu-enkephalin stimulate the hormonal function of the thymic epithelium. These findings lead to the general concept that the modulatory role of endogenous opioids on the immune system is not restricted to lymphocytes but can also take place at the level of cells belonging to T-cell differentiating microenvironments.

Production of substances with thymosin-like activity by B- and T-lymphocytes.

The authors investigated the ability of various lymphocyte subpopulations to synthesize substances with thymosin-like activity under the influence of thymostimulin, a preparation of active thymic factors. Experiments carried out on T- and B-mice revealed that only T-lymphocytes synthesized thymosin-like substances in response to thymostimulin administration. Thus induced substances differed significantly from those which ensure the serum activity of normal animals in that their thermostability is by far greater. The feasibility was also explored of inducing by thymosin the in vitro synthesis of substances with thymosin-like activity in cells derived from a variety of lymphoid formations of thymectomized mice. The serum of thymectomized lethally irradiated recipients of lymph node and spleen cells pretreated with thymostimulin was found to contain, 4 h after the transfer, relatively high levels of substances with thymosin-like activity. Contrariwise, the pretreatment of bone marrow cells with thymostimulin resulted in declined levels of substances with thymosin-like activity in recipient sera as compared to those in B-mice which were given untreated bone marrow cells. The incubation of bone marrow cells in a medium containing substances with thymosin-like activity caused a decrease in that activity. Thus, the biologically active thymic factors were shown to induce the synthesis by T-cells of substances with thymosin-like activity.

Phenotypic characterization of murine thymic microenvironments.

The thymus provides the necessary microenvironments for the differentiation of T lymphocytes. Thymic non-lymphoid cells, such as epithelial cells, macrophages and interdigitating cells are thought to promote sequential stages in T cell differentiation. However, their specific role in each step of T cell differentiation remains to be established. With the development of new monoclonal antibodies it has now become possible to characterize the different thymic stromal cell types. In this review, various aspects of thymic stromal cells and their functions in T cell differentiation are discussed, such as: (1) phenotypic analysis of stromal cells in situ; (2) the application of new "chimeric' monoclonal antibodies which "link' developing thymocytes and stromal cells; (3) perturbation of thymic microenvironments after cyclosporin-A treatment; (4) perturbation of thymic microenvironments in new transgenic mouse lines; (5) phenotypic analysis of in vitro growing stromal cell lines.

Studies on the thymus in Chagas' disease. I. Changes in the thymic microenvironment in mice acutely infected with Trypanosoma cruzi.

Previous observations demonstrated severe thymocyte depletion in mice undergoing acute Chagas' disease. These data led us to investigate the status of the thymic microenvironment in these animals. Young adult C57BL/6 and C3H/HeJ mice were infected i.p. with 10(5) blood-derived trypomastigote forms of Trypanosoma cruzi (CL strain) and killed 7-14 days after infection. Sera were then analyzed for thymic hormone (thymulin) levels, and frozen thymus sections were studied by immunohistochemistry for the expression of functional antigens (thymulin and Ia), the distribution of distinct thymic epithelial cell subsets and extracellular matrix components. Infected mice exhibited a transient decrease in thymulin production and those with severe thymic atrophy showed a denser Ia-bearing cellular network. In addition, an abnormal localization of the TR5 and CK18 antigens restricted to the medullary and cortical TEC subsets, respectively, was observed. Furthermore, an increase in the basement membrane proteins was detected within thymic lobules. We suggest that the thymic microenvironment is also affected during T. cruzi infection, extending the concept that the thymus should be regarded as a target in Chagas' disease.

Neuroendocrine control of thymic hormonal production. I. Prolactin stimulates in vivo and in vitro the production of thymulin by human and murine thymic epithelial cells.

The thymic epithelium is responsible for the secretion of thymic peptides, which intervene in some steps of intra- and extrathymic T cell differentiation. Recent data suggest that thymic hormone secretion is modulated by the neuroendocrine network, comprising thyroid, adrenals, and gonads. However, the role of the pituitary gland in this regulation is still poorly understood. In the present paper we studied the in vivo and in vitro influences of PRL on the secretion of thymulin, one of the chemically defined thymic hormones, by thymic epithelial cells (TEC). When injected daily (20-100 micrograms/20 g) in young or old C57BL/6 mice, PRL induced a specific increase in thymulin synthesis and secretion, respectively, measured by the number of thymulin-producing cells in the thymus and the peripheral levels of the hormone. This stimulation was dose dependent and reversible after the end of treatment. Similar findings have been made in animals with pituitary dwarfism, known to have low levels of circulating thymulin. This stimulatory effect was also observed in primary cultures of human and mouse TEC when PRL (10(-7) to 10(-8) M) was applied to culture supernatants, thus suggesting that PRL could act directly on TEC. In addition, we induced in vivo experimental hypoprolactinemia, treating mice with bromocriptine, a dopamine receptor agonist that inhibits pituitary PRL secretion. Bromocriptine treatment (100-200 micrograms/20 g) yielded a significant decrease in thymulin secretion that could be reversed by coincident treatment with PRL. In the light of previous observations that bovine GH can also increase thymulin production in aged dogs, we performed a series of experiments in vitro to evaluate whether GH has a direct effect on TEC. We observed that only human GH preparations that are known to have a PRL-like effect were efficient in stimulating thymulin biosynthesis and release into the culture supernatants. The effects of PRL on TEC were not restricted to thymic hormone production. We observed that TEC proliferation, as well as the numbers of a TEC subset defined by the expression of cytokeratins 3 and 10, could also be increased by PRL treatment. All these findings show that the pituitary gland directly affects TEC in terms of cytoskeletal and secretory protein expression as well as cell cycle.

Do epidermal cells produce thymic hormones in vivo? An immunohistochemical study using anti-thymic hormone antibodies.

Cultured human epidermal cells have been shown to produce soluble factors endowed with T cell differentiating activities. In addition, the presence of thymopoietin and FTS/thymulin-like factors has been reported in normal human and mouse epidermis using immunohistochemical methods and anti-thymic hormone antibodies. The present study was conducted to re-evaluate the presence of thymic hormones in normal epidermal cells using a panel of monoclonal antibodies (mAbs) and rabbit antisera to several well characterized thymic factors. The reactivity of the following antibodies was tested by indirect immunofluorescence on human and mouse tissue sections: a) two anti-FTS/thymulin mAbs; b) one anti-FTS/thymulin rabbit antiserum; c) one anti-thymopoietin rabbit antiserum; d) one anti-thymosin alpha 1 mAb. Our results show that: 1) all five antibodies reacted with human and/or mouse thymic epithelial cells; 2) none of the 3 antithymic hormone mAbs (2 anti-FTS/thymulin and 1 anti-thymosin alpha 1 mAbs) reacted with normal skin; 3) only 2 out of 5 antibodies, namely the anti-FTS and anti-thymopoietin antisera cross-reacted with mouse and human epidermis and labeled keratinocytes, as previously reported; these latter 2 antibodies also stained nude mouse epidermal cells and labeled non-thymic, non-epidermal normal mouse epithelial tissues, suggesting that the cross-reactive epitope is common to a number of epithelial cells; 4) the antigen defined by the anti-FTS and anti-thymopoietin antisera was not related to keratins, since absorption experiments using purified human epidermal keratins failed to abolish staining of the epidermis. We conclude from this study that epidermal cells do not produce in vivo the well characterized thymic hormones: FTS/thymulin, thymopoietin and thymosin alpha 1. The precise nature of the antigenic structure recognized within epidermis by the anti-FTS and anti-thymopoietin antibodies remains to be defined.

Estudio histológico y nueva interpretación de las estructuras queratinizadas en las amigdalas palatinas humanas / Histological study and new interpretation of the keratinized structures in the human palatin tonsils

Actualmente se reconoce a la epidermis como un órgano adscrito al sistema inmunológico, habiéndose comprobado que sus células epiteliales suministran el sustrato para la maduración post-tímica de los linfocitos T. Ya que existen muchas analogías entre los queratinocitos epidérmicos y las células reticuloepiteliales del timo, similitudes no sólo morfológicas sino bioquímicas e inmunológicas en donde la queratina parece jugar un rol trascendente, hemos examinado las zonas queratinizadas en amígdalas palatinas obtenidas por extirpación quirúrgica, con el fin de determinar la relación entre los fenómenos inflamatorios y la presencia de formaciones que se asemejan a los corpúsculos tímicos de Hassall. Dichas formaciones, que dan las reacciones histológicas e histoquímicas propias de la queratina, se ubican tanto en regiones alejadas como cercanas al lumen de las criptas amigdalares, y con mayor frecuencia en áreas desprovistas de inflamación, a juzgar por la escasez de polimorfonucleares y demás células asociadas al proceso las que, sin embargo, son frecuentes en otras regiones del epitelio. Nuestras comprobaciones nos permiten concluir que estas estructuras no representan zonas de queratinización superficial en respuesta a estímulos irritativos, y que su presencia en este lugar podría obedecer a una razón funcional semejante a la que condiciona la formación de los corpúsculos tímicos

Anti-islet cellular and humoral immunity, T-cell subsets, and thymic function in type I diabetes.

UNLABELLED: Peripheral lymphocyte subsets were enumerated, using OKT monoclonal sera, in 56 diabetic (43 adults and 13 children) and 20 control subjects. Concomitantly, anti-islet humoral and cellular immunity was tested in vitro and serum thymulin level was measured. In the newly diagnosed patients (less than 30 days; 18 cases), the percent of OKT4+ and OKT8+ cells was reduced, the OKT8+ depletion being particularly pronounced in children. Tests for cellular immunity were positive in 83% of the newly diagnosed diabetic subjects and anti-islet cytotoxic antibodies were detected in 50%. The serum thymulin level was decreased in 2 children. Later on in the course of the disease, a marked reduction in OKT3+, OKT4+, and OKT8+ cell percentage was observed, the mean OKT4/OKT8 ratio being normal or lower than normal. The percent of antibody-positive sera rose to 64%, while anti-islet cellular immunity was detectable in 54%. When extrapancreatic manifestations of probable autoimmune nature were present, anti-islet cellular immunity was detected in 100% of cases, accompanied by cytotoxic antibodies in 54%. CONCLUSIONS: (1) the magnitude of T-cell depletion and/or imbalance in diabetic subjects depended mainly on the duration of the disease, (2) anti-islet cellular immunity was the anomaly most frequently detectable, and (3) a decrease in serum thymulin level was infrequently detected.

Endocrine control of thymic serum factor production in young-adult and old mice.

The influence of different endocrinological manipulations on the blood concentration of serum thymic factor (FTS) was studied in young-adult and old mice. Among the experimentally induced endocrinopathies in youth, hypothyroidism and diabetes caused strong reductions of FTS levels, which were restored to normal by the appropriate hormonal substitutive therapy. Removal of adrenals or gonads has no significant effect on FTS level. Old mice, which show undetectable levels of FTS and low levels of thyroxine, can regain the capacity to produce FTS, provided they are treated with thyroxine. The variations of FTS blood levels in the course of endocrinological manipulations were due to a direct or indirect effect exerted on the recipient thymus. Hormonal treatment of thymectomized mice did not induce any FTS-like activity in their sera, nor did hormones interfere in vitro with the bioassay used to test for FTS. These data suggest that the neuroendocrine balance modulates the synthesis and/or the release of FTS from the thymus during the whole life of the organism and that the decline of FTS production with advancing age is largely dependent on age-associated endocrinological imbalances.

Bone marrow transplantation--an expanding approach to treatment of many diseases.

Thus, we can conclude that marrow transplantation has already influenced medical practice greatly. It has offered a treatment which often cures patients of more than 20 otherwise lethal diseases. The treatment so horrendously difficult and dangerous at first has already been greatly improved, simplified, and made much safer. The availability of a suitable donor has been much extended and real progress has been made in prevention and perhaps even in treatment of graft-versus-host disease. This has made possible the option of marrow transplantation for every patient in whom we think the treatment may be beneficial. The problem underlying many cases of interstitial pneumonia has been identified and patients are already benefitting clinically from this progress. Progress has also been made which promises antiviral therapy which could reduce, prevent, and ultimately eliminate the intercurrent virus infections which limit the applicability of marrow transplantation, especially for children with severe immunodeficiencies. I do not know how far this line of investigation can be taken. However, just as we have learned stepwise to use marrow transplants from matched siblings to treat many diseases, to use fetal liver in place of bone marrow, to employ matched relative donors when a matched sibling is not available, and, finally, even to use parental donors to achieve correction of SCID, we now have good reason to believe that, ultimately, we can use marrow transplantation without fear of GVHD to address many additional genetically determined and acquired diseases; certainly, for those diseases that involve any of the cells that are derived from bone marrow cells, and perhaps for those attributable even to cells of other organs and tissues, the functions of which are, in whole or in part, a consequence of interactions of marrow-derived cells and cells of ectodermal or endodermal origin, marrow transplantation may be useful. To us, the future of marrow transplantation as a major modality of treatment or prevention of many diseases, including hemoglobinopathesis, immunodeficiencies, hematologic abnormalities, abnormalities of function of marrow-derived cells, and even inborn errors of function of cells of organs and tissues not of marrow origin, seems bright, indeed. Further, with the capacity to introduce resistance genes against viruses and malignancies, autoimmune diseases, and diseases dependent on anomalies of immune response genes, marrow transplantation for many other diseases seems a more remote possibility.(ABSTRACT TRUNCATED AT 400 WORDS)