Gut Lymph Nodes Research Articles

Case of a CD3 Negative Hepatosplenic T-Cell Lymphoma: Diagnostic and Therapeutic Challenges

Hepatosplenic T-cell lymphomas (TCLs) are a rare, aggressive subset of TCLs, accounting for less than 5% of all peripheral T-cell and natural killer (NK) cell lymphomas. We report the case of a CD3 negative hepatosplenic T-cell lymphoma in a 42-year-old female, who presented with left-sided abdominal pain. She underwent a liver biopsy that showed marked abnormal sinusoidal lymphoid infiltration. PET scan revealed increased splenic and pharyngeal lymph node uptake. Immunophenotype was remarkable for negative CD3, gamma delta T-cell receptor, and alpha beta-T-cell receptor expression. She received 6 cycles of DA-EPOCH, had primary refractory disease and then underwent palliative splenectomy secondary to painful necrosis. Then, she was started on pralatrexate as a single agent and then in combination with romidepsin as a potential bridge to an allogeneic stem cell transplantation from her sibling.

Lymph node segregation for tolerance or inflammation

Lymph node segregation for tolerance or inflammation

Novel Targeting to XCR1+ Dendritic Cells Using Allogeneic T Cells for Polytopical Antibody Responses in the Lymph Nodes.

Vaccination strategy that induce efficient antibody responses polytopically in most lymph nodes (LNs) against infections has not been established yet. Because donor-specific blood transfusion induces anti-donor class I MHC antibody production in splenectomized rats, we examined the mechanism and significance of this response. Among the donor blood components, T cells were the most efficient immunogens, inducing recipient T cell and B cell proliferative responses not only in the spleen, but also in the peripheral and gut LNs. Donor T cells soon migrated to the splenic T cell area and the LNs, with a temporary significant increase in recipient NK cells. XCR1+ resident dendritic cells (DCs), but not XCR1− DCs, selectively phagocytosed donor class I MHC+ fragments after 1 day. After 1.5 days, both DC subsets formed clusters with recipient CD4+ T cells, which proliferated within these clusters. Inhibition of donor T cell migration or depletion of NK cells by pretreatment with pertussis toxin or anti-asialoGM1 antibody, respectively, significantly suppressed DC phagocytosis and subsequent immune responses. Three allogeneic strains with different NK activities had the same response but with different intensity. Donor T cell proliferation was not required, indicating that the graft vs. host reaction is dispensable. Intravenous transfer of antigen-labeled and mitotic inhibitor-treated allogeneic, but not syngeneic, T cells induced a polytopical antibody response to labeled antigens in the LNs of splenectomized rats. These results demonstrate a novel mechanism of alloresponses polytopically in the secondary lymphoid organs (SLOs) induced by allogeneic T cells. Donor T cells behave as self-migratory antigen ferries to be delivered to resident XCR1+ DCs with negligible commitment of migratory DCs. Allogeneic T cells may be clinically applicable as vaccine vectors for polytopical prophylactic antibody production even in asplenic or hyposplenic individuals.

Compartmentalized gut lymph node drainage dictates adaptive immune responses.

The intestinal immune system has the challenging task of tolerating foreign nutrients and the commensal microbiome, while excluding or eliminating ingested pathogens. Failure in such balance leads to severe diseases such as inflammatory bowel diseases (IBD), food allergies or invasive gastrointestinal infections1. Multiple immune mechanisms are therefore in place to maintain tissue integrity, including balanced generation of effector T (TH) cells and FOXP3+ regulatory T (pTreg) cells, which mediate resistance to pathogens and regulate excessive immune activation, respectively1–4. The gut–draining lymph nodes (gLNs) are critical sites for orchestrating adaptive immunity to luminal perturbations5–7. However, how they manage to simultaneously support tolerogenic and inflammatory reactions is incompletely understood. Here we report that gLNs are immunologically unique according to the functional gut segment they drain. Stromal and dendritic cell gene signatures as well as T cell polarization against the same luminal antigen differed between gLNs, the proximal small intestine–draining gLNs preferentially giving rise to tolerogenic and the distal gLNs to pro-inflammatory T cell responses. This segregation permitted targeting distal gLNs for vaccination and maintenance of duodenal pTreg cell induction during colonic infection. Conversely, the compartmentalized dichotomy was perturbed by surgical removal of select distal gLNs and duodenal infection, impacting both lymphoid organ and tissue immune responses. Our findings reveal that the conflict between tolerogenic and inflammatory intestinal responses is in part resolved by discrete gLN drainage, and encourage gut segment-specific antigen targeting for therapeutic immune modulation.

Microbiota of the Gut-Lymph Node Axis: Depletion of Mucosa-Associated Segmented Filamentous Bacteria and Enrichment of Methanobrevibacter by Colistin Sulfate and Linco-Spectin in Pigs.

Microorganisms are translocated from the gut to lymphatic tissues via immune cells, thereby challenging and training the mammalian immune system. Antibiotics alter the gut microbiome and consecutively might also affect the corresponding translocation processes, resulting in an imbalanced state between the intestinal microbiota and the host. Hence, understanding the variant effects of antibiotics on the microbiome of gut-associated tissues is of vital importance for maintaining metabolic homeostasis and animal health. In the present study, we analyzed the microbiome of (i) pig feces, ileum, and ileocecal lymph nodes under the influence of antibiotics (Linco-Spectin and Colistin sulfate) using 16S rRNA gene sequencing for high-resolution community profiling and (ii) ileocecal lymph nodes in more detail with two additional methodological approaches, i.e., cultivation of ileocecal lymph node samples and (iii) metatranscriptome sequencing of a single lymph node sample. Supplementation of medicated feed showed a local effect on feces and ileal mucosa-associated microbiomes. Pigs that received antibiotics harbored significantly reduced amounts of segmented filamentous bacteria (SFB) along the ileal mucosa (p = 0.048; 199.17-fold change) and increased amounts of Methanobrevibacter, a methanogenic Euryarchaeote in fecal samples (p = 0.005; 20.17-fold change) compared to the control group. Analysis of the porcine ileocecal lymph node microbiome exposed large differences between the viable and the dead fraction of microorganisms and the microbiome was altered to a lesser extent by antibiotics compared with feces and ileum. The core microbiome of lymph nodes was constituted mainly of Proteobacteria. RNA-sequencing of a single lymph node sample unveiled transcripts responsible for amino acid and carbohydrate metabolism as well as protein turnover, DNA replication and signal transduction. The study presented here is the first comparative study of microbial communities in feces, ileum, and its associated ileocecal lymph nodes. In each analyzed site, we identified specific phylotypes susceptible to antibiotic treatment that can have profound impacts on the host physiological and immunological state, or even on global biogeochemical cycles. Our results indicate that pathogenic bacteria, e.g., enteropathogenic Escherichia coli, could escape antibiotic treatment by translocating to lymph nodes. In general ileocecal lymph nodes harbor a more diverse and active community of microorganisms than previously assumed.

Treatment and prognosis of 264 patients with hypopharyngeal carcinoma

Objective: To investigate the key factors influencing the prognosis of hypopharyngeal carcinoma and the therapeutic methods improving the efficacy of treatments for hypopharyngeal carcinoma. Methods: Two hundred and sixty-four cases of hypopharyngeal squamous cell carcinoma treated from May 2010 to May 2015 were analyzed retrospectively. There were 211 cases of pyriform sinus carcinoma, 37 cases of posterior pharyngeal wall carcinoma, and 16 cases of postcricoid carcinoma. According to UICC 2002 criteria, 2 cases were for stage Ⅰ, 14 for stage Ⅱ, 32 for stage Ⅲ and 216 for stage Ⅳ. Postoperative circumferential defects existed in 112 (42.4%) cases, and 86 of them were reconstructed with free jejunum transplantation. Among all cases, 54 patients (20.5%) had the preservation of laryngeal functions after surgery and 210 patients (79.5%) with total laryngectomy; 238 cases (90.2%) underwent bilateral cervical lymph node dissection and 203 patients received posterior pharyngeal lymph node exploration and dissection, with positive metastases for posterior pharyngeal lymph nodes in 36 cases (17.7%). Eight cases with cervical lymph node metastasis extensively involving the soft tissue, prevertebral fascia or encases carotid artery received preoperative radiotherapy of 50 Gy. After surgery 13 patients received concurrent radiotherapy and chemotherapy, 337 underwent adjuvant radiotherapy with a dose of 50-60 Gy each, and 14 patients did not receive radiotherapy or did not completed their radiotherapy programs. SPSS 13.0 saftware was used to analyze the data. Results: All patients were followed up for more than 2 years. With Kaplan-Meier method, the 2-, 3- and 5-years survival rates were 69.6%, 62.8% and 51.3%, respectively. There were significant differences in 3-year survival rates between T1-2 group (75.5%) and T3-4 group (59.2%) (χ(2)=4.282 P=0.039), N0 group (81.6%) and N+ group (58.2%) (χ(2)=6.802 P=0.009), laryngeal functions preserved (81.8%) and unpreserved group (58.9%) (χ(2)=5.314 P=0.021). Multivariate Logistic regression analysis showed that cervical lymph node metastasis was an independent prognostic factor (P=0.027). The success rate of free jejunum transplantation was 98.8%. Local recurrence, cervical lymph node recurrence, second primary cancer, and distant metastasis accounted respectively for 11.2%, 18.8%, 12.5% and 45.0% of death cases. Conclusions: The prognosis-associated factors for hypopharyngeal carcinoma should be taken into account, including the evaluation of the carcinogenesis of the mucosal area, early screening of premalignant lesion or second primary cancer in the esophagus and dissection of the posterior pharyngeal lymph nodes, which will help to improve the local control rate and recent survival rate in patients with hypopharyngeal cancer.

Re-emergence of bovine haemorrhagic septicaemia in Hungary.

This paper reports an outbreak of haemorrhagic septicaemia caused by Pasteurella multocida B:2 in beef calves, a disease that has not been described in the Hungarian literature since 1943, and has not been reported to the World Organisation For Animal Health (OIE) since 1970. Acute haemorrhagic septicaemia was confirmed in beef calves on one small farm, and was suspected on two further nearby holdings with concomitant unexplained losses. The source of the infection could not be determined. Apart from a short duration of depression and loss of appetite, the affected calves developed characteristic distal limb oedema. Gross findings in two calves submitted for laboratory examinations included subcutaneous oedema and haemorrhages on serous membranes, and in one case severe pharyngeal lymph node enlargement was observed. Histological examinations revealed lesions characteristic of septicaemia. Moderate to large amounts of Pasteurella antigens were detected in all organs tested by immunohistochemistry. Two isolates of P. multocida (Pm240, Pm241) were cultured from these cases and examined in detail. These were identified as P. multocida ssp. multocida biovar 3. Both were toxA negative and belonged to serotype B:2. Multilocus sequence typing was used to assign these to a new sequence type (ST64) that is closely related to other haemorrhagic septicaemia causing strains of P. multocida regardless of the host.

A Simian Immunodeficiency Virus-Infected Macaque Model To Study Viral Reservoirs That Persist during Highly Active Antiretroviral Therapy

The treatment of human immunodeficiency virus type 1 (HIV-1) infection with highly active antiretroviral therapy (HAART), a combination of three or more antiretroviral drugs, suppresses viremia below the clinical limit of detection (50 HIV-1 RNA copies/ml), but latently infected resting CD4(+) T cells serve as lifelong reservoirs, and low-level viremia can be detected with special assays. Recent studies have provided evidence for additional reservoirs that contribute to residual viremia but are not present in circulating cells. Identification of all the sources of residual viremia in humans may be difficult. These discoveries highlight the need for a tractable model system to identify additional viral reservoirs that could represent barriers to eradication. In this study, simian immunodeficiency virus (SIV)-infected pig-tailed macaques (Macaca nemestrina) were treated with four antiretroviral drugs to develop an animal model for viral suppression during effective HAART. Treatment led to a biphasic decay in viremia and a significant rise in levels of circulating CD4(+) T cells. At terminal infection time points, the frequency of circulating resting CD4(+) T cells harboring replication-competent virus was reduced to a low steady-state level similar to that observed for HIV-infected patients on HAART. The frequencies of resting CD4(+) T cells harboring replication-competent virus in the pooled head lymph nodes, gut lymph nodes, spleen, and peripheral blood were reduced relative to those for untreated SIV-infected animals. These observations closely parallel findings for HIV-infected humans on suppressive HAART and demonstrate the value of this animal model to identify and characterize viral reservoirs persisting in the setting of suppressive antiretroviral drugs.

Cytokine expression in colostrum-deprived pigs immunized and challenged with Haemophilus parasuis

The expression of several cytokines in spleen, pharyngeal lymph nodes, lung and brain after different immunization procedures and a challenge with 5 × 10 9 CFU of Haemophilus parasuis was compared. Five groups of colostrum-deprived pigs were used: vaccinated with (I) a bacterin, (II) an outer-membrane-protein-vaccine, (III) a recombinant transferring-binding protein B, (IV) exposed to a total dose of 10 5 CFU, and (V) not previously immunized. All pigs in groups III and V died, while all animals in group I, most of group IV and half of group II survived until the end of the experiment. IL-1α was found in significantly higher levels ( p < 0.05) in spleen, lymph nodes and brain of dead pigs, which could be explained by the major severity of lesions in these animals. However, IL-4, IL-10, TNF-α and IFN-γ were expressed in significantly higher levels by survivors (for all the four cytokines in lymph nodes; for IL-4, IL-10 and TNF-α in spleen; for IL-4, TNF-α and IFN-γ in lung, and only for TNF-α in brain), thus suggesting a role of these four cytokines in the adaptive response, which might contribute to protection against H. parasuis infection.

Dangers of restocking T cells

Refilling an empty niche with proliferating CD8+ T cells can cause autoimmune disease, say Tajima et al. (page 1019). Figure 1 Autoimmune colitis (top) caused by homeostatically proliferating CD8+ T cells is resolved in mice injected with anti–IL-6 antibody (bottom). Infusion of naive T cells into an environment where there are few native T cells—such as in patients undergoing cancer therapy—spurs two kinds of proliferation. T cells activated by non-self-peptide/MHC complexes proliferate rapidly, whereas those activated by self-peptide/MHC in the presence of cytokines such as IL-7 and IL-15 proliferate slowly. CD4+ T cells that proliferate by these methods have previously been shown to drive the inflammation seen in several autoimmune diseases. Tajima et al. now find a new variation in homeostatic proliferation of CD8+ T cells that also induces autoimmunity. In gut lymph nodes of T cell–deficient mice, injected CD8+ T cells proliferated rapidly in response to IL-6. This inflammatory cytokine was found at high levels in these lymph nodes, perhaps due to their proximity to the bacterium-laden gut. The mice developed a thicker gut epithelium and lost weight—signs of an autoimmune disease called colitis. T cell–injected mice treated with an IL-6–blocking antibody or with bacterium-depleting drugs, however, remained healthy. The proliferating T cells secreted several inflammatory cytokines, including IL-17. The IL-17 alone seemed to be responsible for the colitis, as mice injected with T cells that were unable to produce IL-17 remained healthy. If these IL-17–producing CD8+ T cells are found in patients suffering from diseases such as colitis, the anti–IL-6 antibody might be a good therapeutic option.

Predominant donor CD103+CD8+ T cell infiltration into the gut epithelium during acute GvHD: a role of gut lymph nodes

The existence of donor effector cell subsets responsible for either gut or skin graft-versus-host disease (GvHD) is still undetermined. We examined the trafficking and role of donor CD8(+) intra-epithelial lymphocytes (IELs) in the gut and skin epithelia concerning alpha E beta 7 integrin (CD103) expression, using a rat acute lethal GvHD model. Most CD103(+) donor cells were CD8(+) and showed a proliferative activity in the target epithelia. On the other hand, activated donor T cells in the host lymphoid tissues did not express CD103, indicating the presence of CD8(+) IEL precursors in the lymphoid tissues that may up-regulate CD103 only after migrating to the target organs. At the late stage of GvHD, while >80% of the donor CD8(+) IELs were CD103(+) in the gut epithelium, both CD4(+) and CD103(+)CD8(+) T cells evenly accumulated in the skin epidermis. The CD103 expression by donor CD8(+) IELs especially in the gut was also correlated with the clinical GvHD manifestations. Furthermore, the selective removal of gut lymph nodes (LNs) but not skin LNs suppressed the infiltration of CD103(+) donor IELs in the gut and alleviated intestinal GvHD. In conclusion, CD103(+)CD8(+) donor T cells predominantly infiltrate into the gut epithelium and are responsible for the manifestations of intestinal GvHD. This pathology is at least partly dependent on the gut LNs.

MAGNETIC RESONANCE IMAGING FEATURES OF PRESUMED NORMAL HEAD AND NECK LYMPH NODES IN DOGS

To document the magnetic resonance imaging appearance of presumed normal lymph nodes of the head and neck in the dog, 91 studies of dogs with no detectable disease in the head acquired on a low-field unit were reviewed. If lymph nodes were imaged, symmetry, signal intensity, homogeneity, and size as well as the relation to the surrounding fat were noted. To improve the description of lymph node topography, we used corresponding E12 plastinated embedded sections of a dog. Compared with surrounding fat, lymph nodes were hypointense in T1 images. In T1-weighted images after intravenous contrast medium lymph nodes were isointense. In T2-weighted images, lymph nodes were slightly hypointense to surrounding fat. In T1 and T2 images, a hypointense band, created by the chemical shift artifact, could be seen at the lymph node-fat boundary along the frequency encoding gradient. In some dogs the lymph node hilus was characterized by vessels indenting the capsule of the lymph node. The facial vein is a consistent landmark to identify mandibular lymph nodes, and the mandibular salivary gland is a useful landmark to localize the medial pharyngeal lymph nodes. The parotid salivary gland or the external acoustic meatus were useful markers to identify the parotid lymph nodes, which were not consistently seen. In some dogs, nodules within the lymphoreticular tissue of the soft palate were seen.

Effects of Mycophenolic Acid on Inosine Monophosphate Dehydrogenase I and II mRNA Expression in White Blood Cells and Various Tissues in Sheep

Mycophenolic acid (MPA) is a mycotoxin commonly found as Penicillium genus secondary metabolite in feedstuffs and silages. Feeding with MPA contaminated silages may modulate the immune system in the farm animals and can cause appetite lost, ketosis, paralysis and abortion. The aim of the present study was to characterize the long-term MPA effect on both the inosine monophosphate dehydrogenase (IMPDH) isoforms I and II mRNA expression in white blood cells (WBC) and various tissue of healthy sheep. In treated animals 300 mg MPA/day/sheep was applied. In all investigated tissues the IMPDH I and II mRNA was abundant: WBC, spleen, thymus, ileum, jejunum, kidney, liver, pharyngeal and mesenterial lymph node. An efficiency-corrected relative quantification of the IMPDH types I and II isoforms mRNA were performed by normalizing with the constant reference gene expression of beta-actin. High IMPDH I mRNA expression levels were seen in kidney > mesenterial lymph node > jejunum > spleen > pharyngeal lymph node. Medium and low abundance was found in ileum > WBC > liver > thymus. Type II mRNA was highly expressed in liver > thymus > jejunum. In pharyngeal lymph node > spleen > ileum > mesenterial lymph node > kidney > WBC medium to low IMPDH II mRNA concentrations were detected. Under MPA treatment the IMPDH I mRNA expression was not significantly regulated in WBC, only trends of down- and upregulation were observed. Surprisingly in jejunum an upregulation could be observed (P < 0.05). In pharyngeal lymph node a tendency to downregulation was shown. This may be due to frequent ruminant activities and frequent exposition of MPA to the pharyngeal lymph nodes. In contrast to type I mRNA expression, IMPDH II mRNA was significantly downregulated in ileum (3.4-fold, P < 0.01) and tendencies in downregulation could be seen in jejunum (5.1-fold, P = 0.14). In addition, significant downregulation of IMPDH II gene expression over the entire feeding experiment could be shown in WBC of MPA-treated animals compared with untreated animals (P < 0.05). In conclusion, the recent study demonstrates that feeding sheep with MPA-contaminated silage did not induce IMPDH I mRNA expression in various tissues and blood, except in jejunum, but has suppressive effects on IMPDH II mRNA expression in WBC and ileum.

Salmonella in slaughter pigs of German origin: an epidemiological study.

The Salmonella prevalence in slaughter pigs of German origin was determined in seven abattoirs located in different regions of the country between February and June 1996. A total of 11,942 pigs delivered to the abattoirs in 752 batches, most of them comprised of pigs from individual finishing farms, was investigated by the bacteriological examination of faecal and gut lymph node samples, as well as of surface swabs taken from the carcasses. Salmonellae were isolated from 3.7% of the faecal samples, 3.3% of the lymph nodes and 4.7% of the surface swabs. The estimated overall prevalence of Salmonellae was 6.2% in the slaughter pigs, ranging between 1.9% and 12% in individual abattoirs. In the samples taken from carcasses, the estimated prevalence of Salmonellae reached 10.3%. 648 out of 752 batches could be included in a statistical analysis. No Salmonellae were detected in nearly 70 percent of the batches included in this analysis (n = 648). High Salmonella prevalences of more than 50 percent positive animals were detected only in 13 batches (2.0%). A statistically significant influence of the duration of the transport of slaughter pigs to the abattoirs or the waiting period in the abattoirs prior to slaughter could not be detected.

Computed tomography in the management of nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is one of the common cancers in China. According to mass surveys, the incidence of NPC in some areas of Guangdong is 39.84/100,000. Due to its high contrast resolution CT has the ability to show not only superficial abnormality but also deep infiltration of the fasciae and muscles of the parapharyngeal region. Computed tomography scanning was performed on more than 1000 patients with NPC in the Tumour Hospital in the 2 years from 1984 to 1986. The role of CT scanning in NPC can be summarised as: (1) detection of primary lesions not accessible to pharyngoscopy; (2) determination of the extent of disease; (3) clinical staging; (4) radiotherapy planning; (5) follow up evaluation; (6) the differentiation of recurrence and radiation damage to the brain; and (7) the demonstration of distant metastasis. In contrast to the concept of jugular chain metastasis via the postero-lateral pharyngeal lymph nodes, our material has demonstrated that the lesion most probably spreads to the carotid sheath area directly from the pharyngeal lesion. The tendency of submucosal spread of NPC is emphasised.

Peripheral blood and mesenteric lymph node lymphocytes in Crohn's disease.

Analysis of peripheral blood lymphocytes from 44 patients with Crohn's disease showed no difference in the proportions of T- and B-cells from those in 38 healthy controls. Analysis revealed no disturbances in relation to duration or to activity of disease or to drug treatment. Lymphocytes from 18 patients with rheumatoid arthritis also showed normal proportions of T- and B-cells. Lymphocytes taken from gut lymph nodes were studied in five patients with Crohn's disease. On comparison with peripheral blood lymphocytes, significantly decreased proportions of T-cells and significantly increased proportions of B-cells were found in lymph nodes draining areas of diseased bowel. No differences were seen in the proportions of T- and B-cells from lymph nodes taken from apparently healthy bowel of the Crohn's patients and of four control subjects without inflammatory bowel disease, though these were different from those in the peripheral blood in both the Crohn's patients and control subjects.

Studies on the pathogenesis of rinderpest in experimental cattle. IV. Proliferation of the virus following contact infection.

Cattle were infected with rinderpest virus by housing them for 24 hr. in stalls containing donor animals which had been reacting to the disease for 3–5 days. They were then transferred to individual clean stalls and killed on the 2nd to 10th days following first exposure. Various tissues were collected, particularly those of the upper and lower respiratory tracts, and their virus content was estimated in calf-kidney tissue cultures.Virus was recovered from 15 of 35 animals tested and in eight of these generalization had occurred, although only two had begun to show a pyrexial response. The stage of the infection could not be predicted from the time that had elapsed following exposure, since early, limited proliferation was encountered on the 3rd to the 10th days.It was considered that seven animals gave indications of the pathways by which natural infection had occurred. In each of these virus proliferation was established very early in the pharyngeal lymph node; in three the submaxillary lymph node was similarly involved and in four the palatal tonsil. It was suggested that these data probably indicated that infection always occurred via the upper respiratory tract.In three cases virus titres were highest in the bronchial or costocervical lymph nodes; this was construed as evidence for the additional involvement of the lower respiratory tract in primary infection.No infectivity could be demonstrated in the mucosae or lung parenchyma associated with the above-mentioned lymph nodes and this, together with previously published data, was accepted as strong presumptive evidence that the infecting virus passes through the mucosae without producing a local lesion or proliferating there. These results were compared briefly with those of Bedson &amp; Duckworth (1963) for rabbit pox.

Increase of Specific and Non-Specific Resistance by the Transplantation of Attenuated Tubercle Bacilli Nodules

Summary Post-mortem examination revealed that the calves no. 131 and 132, recipients of the 9-day-old nodules showed no specific lesions after having been injected intravenously with virulent tubercle bacilli. In the control calf, untreated before the injection of the virulent bacilli, definite processes of miliary tuberculosis were found in the lungs and the thoracic lymph nodes. In calf no. 10,793 from which the nodules had been removed, there was a very pronounced enlargement of the thoracic and pharyngeal lymph nodes, but specific lesions could not be seen either with the naked eye or under the microscope. The degree of resistance left after removal of the two nodules from calf no. 10,793, which had received 10 cg of the less attenuated I.V.A. vaccine, seemed to be greater than the degree of resistance left in a calf from which a nodule formed by subcutaneous injection of only 5 cg of B.C.G. had been removed.