Translocation ofLactobacillus murinus from the gastrointestinal tract

Bacterial translocation is defined as the passage of viable bacteria from the gastrointestinal tract to the mesenteric lymph nodes and other extraintestinal sites. The translocation rate of a newly described species of indigenous bacteria,Lactobacillus murinus, was compared with the translocation rates of indigenousLactobacillus acidophilus and nonindigenousSalmonella enteritidis. Groups of germfree or antibiotic-decontaminated, specific pathogen-free mice were monoassociated with each of these bacterial strains and tested at various intervals for translocation to the mesenteric lymph nodes. The translocation rates of the various bacteria expressed in decreasing order as the numbers of translocating bacteria per gram mesenteric lymph node wereS. enteritidis, L. murinus, andL. acidophilus. The degree of histologic damage to the gastrointestinal mucosa after monoassociation with these strains followed the same pattern. Thus,L. murinus translocates from the GI tract at a surprisingly high rate for an indigenous bacterial strain, and its translocation appears to be associated with mucosal alterations.     

Bacterial translocation from the gastrointestinal tracts of mice receiving immunosuppressive chemotherapeutic agents

Specific pathogen-free (SPF) mice were treated with certain classes of immunosuppressive chemotherapeutic agents to determine if they would promote bacterial translocation from the gastrointestinal tract to the mesenteric lymph node, spleen, or liver. The antimetabolites methotrexate, 5-fluorouracil, and cytosine arabinoside were injected once intraperitoneally into SPF mice, and the mice were tested for bacterial translocation from the gastrointestinal tract. When total organs from the treated mice were compared with the total organs from the control mice, the alkylating agent cyclophosphamide promoted bacterial translocation when injected once intraperitoneally at doses of 100–400 mg/kg. Increasing the number of injections of cyclophosphamide did not increase the incidence of bacterial translocation. The steroid prednisone also promoted bacterial translocation after one intraperitoneal injection of 10–150 mg/kg. Prednisone and cyclophosphamide at various doses appeared to be more effective in promoting bacterial translocation from the gastrointestinal tract than the antimetabolites. The aerobic and facultatively anaerobic bacteria translocating to the various organs were identified asLactobacillus acidophilus, Escherichia coli, Klebsiella pneumoniae, Streptococcus faecalis, Staphylococcus aureus, andProteus mirabilis. Groups of SPF mice also were injected once intraperitoneally with the minimal dose of each chemotherapeutic drug that induced bacterial translocation, and then tested for immune responsiveness toE. coli vaccination. Each of the chemotherapeutic agents at the minimal doses promoting bacterial translocation also suppressed the serum antibody responses to antigens of indigenousE. coli. However, other toxic manifestations of these chemotherapeutic agents also may be involved in promoting bacterial translocation. The promotion of bacterial translocation from the gastrointestinal tract by these chemotherapeutic agents has important implications for the pathogenesis of infectious disease in patients receiving these drugs.     

Endogenous infection in mice with streptozotocin-induced diabetes. A feature of bacterial translocation

Slc:ddY mice that received a single intraperitoneal injection of 200 mg/kg streptozotocin (STZ) were examined for persistency of diabetes (changes of indigenous bacterial floras, and bacterial translocation. Significant diabetes (increase in plasma glucose and decrease in insulin) was recognized 2 weeks after the injection, and persisted for 12 weeks. The numbers of aerobic gram-negative bacilli, staphylococci (including micrococci), and streptococci in caecal and oral floras were significantly increased, but the numbers of anaerobic bacteria in caecal flora were hardly changed. Bacterial translocation of indigenous bacteria to the mesenteric lymph node, lung, or kidney was detectable in some mice 2 weeks after the injection. The incidence of bacterial translocation in these STZ-treated mice then increased; infection caused by several organisms, e.g., Klebsiella pneumoniae, Staphylococcus epidermidis, streptococci, or Lactobacillus sp., occurred in lung, liver, spleen, kidneys, and mesenteric lymph node. No indigenous bacteria were cultured from these organs of control mice. This endogenous infection may have been due to the over population of several bacterial strains caused by disruption of indigenous floras along with depression of immunological function.     

Bacterial translocation from the intestines

Bacterial translocation is defined as the passage of viable bacteria from the gastrointestinal (GI) tract through the mucosal epithelium to other sites, such as the mesenteric lymph nodes, spleen, liver and blood. This paper reviews results from animal models utilized to obtain information concerning the defense mechanisms operating in the healthy host to confine bacteria to the GI tract. Gnotobiotic and antibiotic-decontaminated mice colonized with particular bacteria demonstrated that the indigenous GI flora maintains an ecologic equilibrium to prevent intestinal bacterial overgrowth and translocation from the GI tract. Studies with athymic (nu/nu) mice, thymus-grafted (nu/nu) mice, neonatally thymectomized mice, and mice injected with immunosuppressive agents demonstrated that the host immune system is another defense mechanism inhibiting bacterial translocation from the GI tract. Ricinoleic acid given orally to mice disrupted the intestinal epithelial barrier allowing indigenous bacteria to translocate from the GI tract. Thus, bacterial translocation from the GI tract of healthy adult mice is inhibited by: (a) an intact intestinal epithelial barrier, (b) the host immune defense system, and (c) an indigenous GI flora maintaining ecological equilibrium to prevent bacterial overgrowth. Deficiencies in host defense mechanisms act synergistically to promote bacterial translocation from the GI tract as demonstrated by animal models with multiple alterations in host defenses. Bacterial translocation occurred to a greater degree in mice with streptozotocin-induced diabetes, mice receiving nonlethal thermal injury, and mice receiving the combination of an immunosuppressive agent plus an oral antibiotic than in mice with only a primary alteration in host defenses. The study of bacterial translocation in these complex models suggests that opportunistic infections from the GI tract occur in discrete stages. In the healthy adult animal, bacterial translocation from the GI tract either does not occur or occurs at a very low level and the host immune defenses eliminate the translocating bacteria. Bacterial translocation does take place if one of the host defense mechanisms is compromised, such as a deficiency in the immune response, bacterial overgrowth in the intestines, or an increase in the permeability of the intestinal barrier. In this first stage, the bacteria usually translocate in low numbers to the mesenteric lymph node, and sometimes spleen or liver, but do not multiply and spread systemically.(ABSTRACT TRUNCATED AT 400 WORDS)     

Bacterial translocation can increase plasma corticosterone and brain catecholamine and indoleamine metabolism

The potential contribution of stress-induced bacterial translocation to the activation of the hypothalamo-pituitary-adrenocortical (HPA) axis and brain biogenic amines was assessed. Mice were restrained for various periods, and brain concentrations of tryptophan, catecholamines, serotonin, and their metabolites, plasma corticosterone, and the translocation of viable bacteria from the gastrointestinal tract to the mesenteric lymph nodes, spleen, and liver were measured. Restraint induced the translocation of indigenous gram-positive bacteria in only a small proportion of animals, but translocation of gram-negative bacteria did not occur. Restraint induced short-lived increases in plasma corticosterone and brain amine metabolism, whereas bacterial translocation was slower and persisted long after the HPA axis and neurochemical responses had dissipated. When mice were infected with Salmonella typhimurium, spontaneous translocation occurred and plasma corticosterone, interleukin-6 concentrations, and brain catecholamine and indoleamine metabolism were elevated. These findings indicate that the translocation of indigenous gastrointestinal bacteria did not contribute to the HPA axis and neurochemical changes induced by restraint. However, translocation of nonindigenous S. typhimurium with or without restraint did induce HPA and neurochemical responses.     

Assessment of mouse strain on bacterial translocation from the gastrointestinal tract

The translocation of indigenous bacteria from the gastrointestinal tract to the mesenteric lymphnodes was compared in ten strains of mice. Indigenous Escherichia coli were cultured from the mesenteric lymphnodes of only two of the six mouse strains examined. Thus, spontaneous translocation of indigenous enteric bacteria across the intestinal barrier did not occur to any significant extent in any of the mouse strains examined. Since bacterial overgrowth in the gastrointestinal tract promotes bacterial translocation, bacterial translocation was tested in ten mouse strains including B10 series after antibiotic-decontaminated and subsequent colonization with streptomycin-resistant E. coli C25. E. coli C25 populated the ceca of the mice at levels of 10(8) to 10(9) per gram and translocated to 90-100% of the mesenteric lymphnodes with mean of 10(1.13) to 10(1.86) per mesenteric lymphnode. However, there were no significant differences between mouse strains as to the translocation incidence or the numbers of viable E. coli C25 per mesenteric lymphnode. Thus, genetic differences between mouse strains did not influence bacterial translocation from the gastrointestinal tract to the mesenteric lymphnodes.     

Inhibition of Bacterial Translocation from the Gastrointestinal Tract of Mice Injected with Cyclophosphamide

Effects of intraperitoneal injection of cyclophosphamide, an immunosuppressant, on the degree of bacterial translocation and morphological changes of Peyer's patches (PP) in the intestine were investigated with antibiotic-decontaminated SPF mice and germfree mice monoassociated with Escherichia coli C25. It has been reported that treatment with cyclophosphamide induces bacterial translocation. Cyclophosphamide treatment in this study, however, significantly decreased E. coli C25 translocation from the gastrointestinal tract to the mesenteric lymph nodes (MLN), although the numbers of lymphoid cells, especially B cells, in the PP, MLN, and spleen were remarkably reduced. Four injections of cyclophosphamide at a dose of 100 mg/kg inhibited bacterial translocation more than one injection at a dose of 200 mg/kg in SPF mice. Germfree mice, however, treated with one dose of 200 mg/kg showed the same inhibition of bacterial translocation as those given 100 mg/kg four times. In cyclophosphamide-treated mice, lymph follicles in the PP were obviously smaller than those in control mice, M-cells were similar in appearance to absorption epithelial cells except for short microvilli, and immune cells among the M-cells had disappeared. These data suggested that inhibition of bacterial translocation in mice treated with cyclophosphamide may be the result of morphological and physiological changes of epithelial cells in the gastrointestinal tract, especially M-cells, as a point of entry of invading bacteria, independent of the changes in immunological function. Received: 16 November 1995 / Accepted: 12 December 1995     

Trichinella spiralis: the influence of short chain fatty acids on the proliferation of lymphocytes, the goblet cell count and apoptosis in the mouse intestine

This study was carried out to determine the influence of short chain fatty acids (SCFA) on spleen and mesenteric lymph node lymphocyte proliferation, goblet cells and apoptosis in the mouse small intestine during invasion by Trichinella spiralis. BALB/c mice were infected with 250 larvae of T. spiralis. An SCFA water solution containing acetic, propionic and butyric acids (30:15:20 mM) was administered orally starting 5 days before infection and ending 20 days post infection (dpi). Fragments of the jejunum were collected by dissection 7 and 10 dpi, and were examined for apoptotic cells in the lamina propria of the intestinal mucosa, and for goblet cells. The proliferation index of the cultured spleen and mesenteric lymph node lymphocytes with MTT test was also determined. The orally administered SCFA solution decreased the proliferation of mesenteric lymph node lymphocytes in the mice infected with T. spiralis at both examination times, but did not influence the proliferative activity of the spleen cells. Seven dpi, both in the spleen and mesenteric lymph nodes, the highest proliferation index of concanavalin A (Con A)-stimulated lymphocytes was found in the group of uninfected animals receiving SCFA animals. This tendency could still be seen 10 dpi in the mesenteric lymph nodes but not in the spleen, where the proliferation index in this group had significantly decreased. In vitro studies revealed, that butyric and propionic acids added to the cell cultures suppressed the proliferation of Con A-stimulated mesenteric lymph nodes and spleen lymphocytes taken from uninfected and T. spiralis-infected mice. Acetic acid stimulated proliferation of splenocytes taken from uninfected mice but did not affect lymphocyte proliferation in mesenteric lymph nodes from uninfected or infected mice. Orally administered SCFA increased the number of goblet cells found in the epithelium of the jejunum 7 dpi, but this number had decreased 10 dpi. The number of apoptotic cells in the lamina propria of the intestinal mucosa of animals infected with the T. spiralis and receiving SCFA was also lower, particularly 10 dpi. The above results show that SCFA can participate in the immune response during the course of trichinellosis in mice.     

Low translocation of Bacillus thuringiensis israelensis to inner organs in mice after pulmonary exposure to commercial biopesticide

Translocation of viable cells from a Bacillus thuringiensis israelensis-based biopesticide to inner organs in a mouse model was studied. Mice were exposed to the originally formulated product through the lungs and gastrointestinal tract by intratracheal instillation. Colony forming units (CFU) were grown from lungs, caecum, spleen and liver on Bacillus cereus-specific agar (BCSA) after 24 h and finally determined to be biopesticide strain B. t. israelensis by large plasmid profile. No CFU were found in spleen or liver of the control mice or in any aerosol background or material. We have shown that viable cells from the commercial product can translocate to spleen and liver of immunocompetent mice in a dose-dependent manner. Furthermore, we discuss the methods of exposure and how bacterial translocation should be taken into consideration when evaluating the safety of novel or reintroduced biopesticides in the future.     

In vitro development of a primary antibody response with lymph node cells.

Utilizing a variety of lymphoid tissues from three common laboratory species, comparative studies were performed to investigate the competence of the dissociated cells to respond to a heterologous erythrocyte with the development of specific plaque-forming cells. Dissociated spleen cells harvested from BDF1 mice consistently developed specific plaque-forming cells (PFC) to sheep red blood cells (SRBC), while hamster spleen cells inconsistently developed specific antibody-forming cells to SRBC. Under identical conditions, guinea pig spleen cells did not develop significant numbers of PFC to SRBC. However, lymph node cell cultures of all three species tested yielded specific PFC. In the mouse and hamster lymph node cell cultures, the yield of PFC per culture or per 10⁶ recovered viable cells was always greater than the yield from companion spleen cell cultures. Guinea pig mesenteric lymph node cell cultures developed the major PFC response to SRBC, while both mesenteric and peripheral lymph node cell cultures from hamsters were equivalent in their response to SRBC. The data demonstrate that it is possible to develop a primary antibody response to SRBC in vitro utilizing normal endogenous hamster or guinea pig lymphoid cells, if lymph nodes are the source of cells.     

Saccharomyces cerevisiae strain UFMG 905 protects against bacterial translocation, preserves gut barrier integrity and stimulates the immune system in a murine intestinal obstruction model

Probiotic is a preparation containing microorganisms that confers beneficial effect to the host. This work assessed whether oral treatment with viable or heat-killed yeast Saccharomyces cerevisiae strain UFMG 905 prevents bacterial translocation (BT), intestinal barrier integrity, and stimulates the immunity, in a murine intestinal obstruction (IO) model. Four groups of mice were used: mice undergoing only laparotomy (CTL), undergoing intestinal obstruction (IO) and undergoing intestinal obstruction after previous treatment with viable or heat-killed yeast. BT, determined as uptake of ^99mTc-E. coli in blood, mesenteric lymph nodes, liver, spleen and lungs, was significantly higher in IO group than in CTL group. Treatments with both yeasts reduced BT in blood and all organs investigated. The treatment with both yeasts also reduced intestinal permeability as determined by blood uptake of ^99mTc-DTPA. Immunological data demonstrated that both treatments were able to significantly increase IL-10 levels, but only viable yeast had the same effect on sIgA levels. Intestinal lesions were more severe in IO group when compared to CTL and yeasts groups. Concluding, both viable and heat-killed cells of yeast prevent BT, probably by immunomodulation and by maintaining gut barrier integrity. Only the stimulation of IgA production seems to depend on the yeast viability.     

Thymus dependency of cells involved in transfer of delayed hypersensitivity to listeria monocytogenes in mice

Delayed-type hypersensitivity (DH) to Listeria antigens was induced in inbred C3Hf/Umc mice by intravenous injection of a sublethal dose of viable Listeria monocytogenes. Bone marrow, spleen, and lymph node cells from the immune mice were capable of passive transfer of DH to syngeneic neonatally thymectomized or lethally (900 R) irradiated recipients. Immune thymus cells as well as immune serum were ineffective in transferring DH to irradiated animals. In vitro treatment with antitheta isoantibody (anti-θ) and complement abolished the capacity of spleen and bone marrow cells from immune donors to transfer DH to irradiated hosts, indicating the thymus dependency of this cell population. The results with bone marrow indicate the existence of a small, but biologically significant, thymus-dependent population in this tissue.     

The analysis of the defense mechanism against indigenous bacterial translocation in X-irradiated mice

The defense mechanism against indigenous bacterial translocation was studied using a model of endogenous infection in X-irradiated mice. All mice irradiated with 9 Gy died from day 8 to day 15 after irradiation. The death of mice was observed in parallel with the appearance of bacteria from day 7 in various organs, and the causative agent was identified to be Escherichia coli, an indigenous bacterium translocating from the intestine. Decrease in the number of blood leukocytes, peritoneal cells and lymphocytes in Peyer's patches or mesenteric lymph nodes was observed as early as 1 day after irradiation with 6 or 9 Gy. The mitogenic response of lymphocytes from various lymphoid tissues was severely affected as well. The impairment of these parameters for host defense reached the peak 3 days after irradiation and there was no recovery. However, in vivo bactericidal activity of Kupffer cells in mice irradiated with 9 Gy was maintained in a normal level for a longer period. It was suggested that Kupffer cells play an important role in the defense against indigenous bacteria translocating from the intestine in mice.     

Scanning electron microscopy of homing and recirculating lymphocyte populations

The surface structure of T and B lymphocytes in vivo was investigated using scanning electron microscopy. For these studies the spleen and mesenteric lymph node of mice enriched for B lymphocytes (adult thymectomized, lethally irradiated, bone marrow reconstituted mice, B mice) and of mice enriched for T lymphocytes (adult, lethally irradiated, thymocyte transferred mice, T mice) were examined. Both types of lymphocytes demonstrated a smooth cell surface when they were situated in their respective microenvironment, whereas recirculating T and B cells exhibited numerous microvilli on the cell surface. In postcapillary venules, known to be the major sites of entry of lymphocytes in lymph nodes, lymphocytes were in contact with the endothelial wall by means of these microvilli. While passing the endothelial lining, lymphocytes withdrew their microvilli and appeared smooth upon arrival in the lymphatic stroma. It is suggested that microvilli on the surface of lymphocytes play a role in cellular recognition mechanisms.     

Protection against dysentery infection (Shigella sonnei) by cells of peritoneal exudate,spleen, thymus,bone marrow and mesenteric lymph nodes of non-immune and specifically immunized mice

Using wild white mice both as donors and recipients, transfer of cells from peritoneal exudate, spleen, thymus, bone marrow and mesenteric lymph nodes were performed. The cells were isolated from non-immune or immunized mice. Mice were immunized either with living dysenteric bacteria or with various preparations obtained from these bacteria. The protective activity of transferred cells was studied in recipients infected with a lethal dose of a living culture ofShigella sonnei.     

Alteration of intestinal microbial ecology in mice by recombinant interleuken-2

In addition to its beneficial immunostimulatory properties, interleukin-2 (IL-2) has many significant side effects including gastrointestinal (GI) toxicities. Preliminary studies of the effects of IL-2 on GI bacterial translocation suggested that IL-2 altered intestinal bacterial population levels. In order to further define the effects of IL-2 on intestinal microecology, groups of specific pathogen-free C57BL/6 mice were injected subcutaneously twice daily for 5 days with various dosages of human recombinant IL-2 (up to a maximum of 1.6 mg/kg injection) or an equal volume of sterile buffer. One day after the final injections, IL-2 had significantly (P<.05) increased in a dose-dependent fashion the mean cecal population levels of indigenousEscherichia coli, other gram-negative bacilli, streptococci, and staphylococci. Maximum increases above control cecal population levels were more than 10,000-fold forE. coli and streptococci, 209-fold for gram-negative bacilli other thanE. coli, and 93-fold for staphylococci. These changes were completely reversible, with normal cecal population levels 12 days after the last IL-2 injection. IL-2 did not change the total cecal population levels of strictly anaerobic bacteria. Ileal and cecal structures, as assessed by light microscopy, were not altered by the highest dose of IL-2. When incubated in vivo with 1.6 mg/ml of IL-2, the growth of an indigenous strain ofE. coli was not different from growth in broth alone. Thus, IL-2 treatment caused the intestinal overgrowth of common opportunistic aerobic and facultatively anaerobic bacterial pathogens, without altering total population levels of strict anaerobes or affecting intestinal histology.     

Disturbance of lymphocyte circulation byPseudomonas aeruginosa infection in oxazolone-sensitized mice

Pseudomonas aeruginosa infection depresses contact sensitivity to oxazolone in mice. To test whether an altered lymphocyte circulation plays a role in this depression⁵¹Cr-labeled lymphocytes fromP. aeruginosa-infected and oxazolone-sensitized donors were injected intravenously into infected and sensitized recipients, and the radioactivity uptake of several organs was determine. The controls consisted of normal mice receiving labeled lymphocytes from normal donors. While the radioactivity recovered from the liver, spleen, and mesenteric lymph nodes was similar in the test and the control group, significantly more radioactivity was recovered from the draining lymph nodes of infected and sensitized recipients. The concentration of labeled lymphocytes from sensitized donors in the draining lymph nodes of sensitized recipients was 18% greater than that of the controls but 31% lower than that of infected and sensitized animals receiving cells from infected and sensitized donors.P. aeruginosa infection enhances lymphocyte entrapment within the draining lymph nodes of oxazolone-sensitized mice.     

DIFFERENCES IN REUTILIZATION OF THYMIDINE IN HEMOPOIETIC AND LYMPHOPOIETIC TISSUES OF THE NORMAL MOUSE

Swiss Albino mice received a single i.v. injection of ³H-thymidine (TdR) or of ¹²⁵I-deoxyuridine (IUdR). Bone marrow, thymus, spleen and mesenteric lymph node were examined for the efficiency of precursor incorporation into DNA, and for DNA renewal from day 1 to day 8.
TdR is 5–8 times more efficiently incorporated by the different organs in vivo and in vitro than is IUdR. This indicates that the discrimination against IUdR occurs at the level of DNA synthesizing cells.
A diminished DNA turnover rate measured with ³H-TdR in comparison with ¹²⁵I-UdR is interpreted to indicate reutilization of TdR.
TdR reutilization was observed in bone marrow and spleen from at least day 1 on, and in the thymus from day 3 on, following pulse labeling of DNA synthesizing cells. The degree of TdR reutilization appears higher in the thymus (67%) than the bone marrow (43%) and spleen (38%). The mesenteric lymph node indicates either no, or a very low efficiency of TdR reutilization. The data are also consistent with a reutilization equally efficient for TdR and IUdR.
It is suggested that the TdR salvage pathway in hemopoietic tissues is largely localized to single organs which have immediate access to TdR made available by catabolism of DNA. The contribution of TdR from systemic reutilization to the organs studied falls within the limits of error of measurements. Moreover, the TdR salvage pathway especially in the lymph node may involve other DNA breakdown products than nucleosides.     

Digestion of Herring by Indigenous Bacteria in the Minke Whale Forestomach

Northeastern Atlantic minke whales (Balaenoptera acutorostrata) have a multichambered stomach system which includes a nonglandular forestomach resembling that of ruminants. Bacteria from the forestomachs of herring-eating whales were enumerated and isolated in an anaerobic rumen-like culture medium (M8W medium). The total viable population of anaerobic bacteria ranged from 73 × 10⁷ to 145 × 10⁸/ml of forestomach fluid (n = 4). Lactobacillus spp. (19.7%), Streptococcus spp. (35.9%), and Ruminococcus spp. (12.8%) were the most common of the bacterial strains (n = 117) isolated by use of M8W medium from the forestomach fluid population of two minke whales. Most of the isolates stained gram positive (93.2%), 62.4% were cocci, and all strains were strictly anaerobic. The population of lipolytic bacteria in one animal, enumerated by use of a selective lipid medium, constituted 89.7% of the viable population. The total viable population of anaerobic bacteria in freshly caught and homogenized herring (Clupea harengus) ranged from 56.7 to 95.0 cells per gram of homogenized prey (n = 3) when M8W medium was used. Pediococcus spp. (30.6%) and Aerococcus spp. (25.0%) were most common of the bacterial strains (n = 72) isolated from the homogenized herring. Most of the bacterial strains were gram positive (80.6%), and 70.8% were cocci. Unlike the forestomach bacterial population, as many as 61.1% of the strains from the herring were facultatively anaerobic. All bacterial strains isolated from the prey had phenotypic patterns different from those of strains isolated from the dominant bacterial population in the forestomach, indicating that the forestomach microbiota is indigenous. Scanning electron microscopic examinations revealed large numbers of bacteria, surrounded by a glycocalyx, attached to partly digested food particles in the forestomach. These data support the hypothesis that symbiotic microbial digestion occurs in the forestomach and that the bacteria are indigenous to minke whales.     

FATE OF THYMOCYTES: STUDIES WITH 125I-IODODEOXYURIDINE AND 3H-THYMIDINE IN MICE

Cortical thymocytes of young adult mice were labeled in situ with radioactive DNA precursors. As a result of cell emigration and cell death, total thymic radioactivity decreased within 8 days to 10% or less of that present on day 1. Accumulation of thymic migrants in peripheral lymphoid organs was estimated by computing the net thymus-derived radioactivity in these tissues. Thymic cell death was assessed by comparing values obtained with ¹²⁵I-UdR to those acquired with ³H-TdR. The results indicate that cortical thymocytes migrate to the spleen, mesenteric lymph node, femurs and intestine; nevertheless, only a small fraction of the activity originally present in the thymus was recovered in these organs; the vast majority of newly formed cortical thymocytes apparently die after a relatively short life span. Exclusive of the fraction which dies in situ, evidence for thymocyte death is seen in bone marrow; however, most migrants appear to terminate in the intestine.