Dominant expansion of CD4+, CD8+ T and NK cells expressing Th1/Tc1/Type 1 cytokines in culture-positive lymph node tuberculosis

Kathamuthu, Gokul Raj; Ramaswamy, Sridhar; Baskaran, Dhanaraj; Babu, Subash

doi:10.1371/journal.pone.0269109

Cited by 8 publications

(7 citation statements)

References 25 publications

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“…Tuberculosis-associated aplastic cytopenia has even been reported in Bacillus Calmette-Guerin vaccination[ 23 ]. Tuberculosis infection can trigger cellular immune responses and lead to the excessive production of proinflammatory cytokines[ 24 , 25 ], thereby inducing immune-mediated hematopoietic injury[ 26 , 27 ]. Gut involvement of tuberculosis infection likely plays a more important role because tuberculosis-induced aplastic cytopenia has been reported merely in disseminated tuberculosis instead of isolated pulmonary tuberculosis.…”

Section: Discussionmentioning

confidence: 99%

Tuberculosis-induced aplastic crisis and atypical lymphocyte expansion in advanced myelodysplastic syndrome: A case report and review of literature

Sun¹,

Yang²,

Xu³

et al. 2023

World J Clin Cases

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BACKGROUND Myelodysplastic syndrome (MDS) is caused by malignant proliferation and ineffective hematopoiesis. Oncogenic somatic mutations and increased apoptosis, necroptosis and pyroptosis lead to the accumulation of earlier hematopoietic progenitors and impaired productivity of mature blood cells. An increased percentage of myeloblasts and the presence of unfavorable somatic mutations are signs of leukemic hematopoiesis and indicators of entrance into an advanced stage. Bone marrow cellularity and myeloblasts usually increase with disease progression. However, aplastic crisis occasionally occurs in advanced MDS. CASE SUMMARY A 72-year-old male patient was definitively diagnosed with MDS with excess blasts-1 (MDS-EB-1) based on an increase in the percentages of myeloblasts and cluster of differentiation (CD)34+ hematopoietic progenitors and the identification of myeloid neoplasm-associated somatic mutations in bone marrow samples. The patient was treated with hypomethylation therapy and was able to maintain a steady disease state for 2 years. In the treatment process, the advanced MDS patient experienced an episode of progressive pancytopenia and bone marrow aplasia. During the aplastic crisis, the bone marrow was infiltrated with sparsely distributed atypical lymphocytes. Surprisingly, the leukemic cells disappeared. Immunological analysis revealed that the atypical lymphocytes expressed a high frequency of CD3, CD5, CD8, CD16, CD56 and CD57, suggesting the activation of autoimmune cytotoxic T-lymphocytes and natural killer (NK)/NKT cells that suppressed both normal and leukemic hematopoiesis. Elevated serum levels of inflammatory cytokines, including interleukin (IL)-6, interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α), confirmed the deranged type I immune responses. This morphological and immunological signature led to the diagnosis of severe aplastic anemia secondary to large granule lymphocyte leukemia. Disseminated tuberculosis was suspected upon radiological examinations in the search for an inflammatory niche. Antituberculosis treatment led to reversion of the aplastic crisis, disappearance of the atypical lymphocytes, increased marrow cellularity and 2 mo of hematological remission, providing strong evidence that disseminated tuberculosis was responsible for the development of the aplastic crisis, the regression of leukemic cells and the activation of CD56+ atypical lymphocytes. Reinstitution of hypomethylation therapy in the following 19 mo allowed the patient to maintain a steady disease state. However, the patient transformed the disease phenotype into acute myeloid leukemia and eventually died of disease progression and an overwhelming infectious episode. CONCLUSION Disseminated tuberculosis can induce CD56+ lymphocyte infiltration in the bone marrow and in turn suppress both normal and leukemic hematopoiesis, resulting in the development of aplastic crisis and leukemic cell regression.

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Section: Discussionmentioning

confidence: 99%

Tuberculosis-induced aplastic crisis and atypical lymphocyte expansion in advanced myelodysplastic syndrome: A case report and review of literature

Sun¹,

Yang²,

Xu³

et al. 2023

World J Clin Cases

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“…A few cases of aplastic cytopenia have been reported to be associated with disseminated tuberculosis[ 14 - 17 ] and even with Bacillus Calmette-Guerin (BCG) vaccination[ 18 ]. Th1 immune responses are the major defense mechanism against tuberculosis[ 19 - 21 ], and Mycobacterium tuberculosis antigens can directly activate Th1 responses[ 21 , 22 ]. Activated Th1 responses lead to production of a large amount of type I inflammatory cytokines[ 19 - 22 ] and thereby suppress host autologous hematopoiesis[ 23 , 24 ], which is the immunological signature of AA and hypoplastic MDS (hMDS)[ 1 , 25 , 26 ].…”

Section: Discussionmentioning

confidence: 99%

“…Although disease phenotypic transformations occurred unexpectedly in this patient, it is not surprising that disseminated tuberculosis can repress leukemic hematopoiesis. Th1 immune responses are the major mechanism in defense against tuberculosis[ 19 - 22 ], and excessive Th1 immune responses can effectively repress granulopoiesis, erythropoiesis and megakaryocytopoiesis[ 23 - 25 ], including leukemic clones[ 61 - 63 ]. During active tuberculosis, our patient manifested aplastic pancytopenia.…”

Section: Discussionmentioning

confidence: 99%

Leukemic transformation during anti-tuberculosis treatment in aplastic anemia-paroxysmal nocturnal hemoglobinuria syndrome: A case report and review of literature

Xiu,

Yang,

et al. 2023

World J Clin Cases

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β cells are the main cells responsible for the hypoglycemic function of pancreatic islets, and the insulin secreted by these cells is the only hormone that lowers blood glucose levels in the human body. β cells are regulated by various factors, among which neurotransmitters make an important contribution. This paper discusses the effects of neurotransmitters secreted by various sympathetic and parasympathetic nerves on β cells and summarizes the mechanisms by which various neurotransmitters regulate insulin secretion. Many neurotransmitters do not have a single source and are not only released from nerve terminals but also synthesized by β cells themselves, allowing them to synergistically regulate insulin secretion. Almost all of these neurotransmitters depend on the presence of glucose to function, and their actions are mostly related to the Ca2+ and cAMP concentrations. Although neurotransmitters have been extensively studied, many of their mechanisms remain unclear and require further exploration by researchers.

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“…Our knowledge of the role of CD4 + T cells in the control of M. tuberculosis infection, in the peripheral blood as well as at the site of infection, is still incomplete. On the other hand, many in vivo and in vitro studies have provided evidence of the significant role of CD8 + T cells in the control of the disease [ 58 ]. In our study, six of eight immunized animals showed a slight increase above the normal range in frequency of CD8 + T cells at 120 days after DNA- hsp65 vaccination.…”

Section: Discussionmentioning

confidence: 99%

Safety and Immunogenicity of an In Vivo Muscle Electroporation Delivery System for DNA-hsp65 Tuberculosis Vaccine in Cynomolgus Monkeys

de Lima,

Leandro,

de Souza

et al. 2023

Vaccines

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A Bacille Calmette–Guérin (BCG) is still the only licensed vaccine for the prevention of tuberculosis, providing limited protection against Mycobacterium tuberculosis infection in adulthood. New advances in the delivery of DNA vaccines by electroporation have been made in the past decade. We evaluated the safety and immunogenicity of the DNA-hsp65 vaccine administered by intramuscular electroporation (EP) in cynomolgus macaques. Animals received three doses of DNA-hsp65 at 30-day intervals. We demonstrated that intramuscular electroporated DNA-hsp65 vaccine immunization of cynomolgus macaques was safe, and there were no vaccine-related effects on hematological, renal, or hepatic profiles, compared to the pre-vaccination parameters. No tuberculin skin test conversion nor lung X-ray alteration was identified. Further, low and transient peripheral cellular immune response and cytokine expression were observed, primarily after the third dose of the DNA-hsp65 vaccine. Electroporated DNA-hsp65 vaccination is safe but provides limited enhancement of peripheral cellular immune responses. Preclinical vaccine trials with DNA-hsp65 delivered via EP may include a combination of plasmid cytokine adjuvant and/or protein prime–boost regimen, to help the induction of a stronger cellular immune response.

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Dominant expansion of CD4+, CD8+ T and NK cells expressing Th1/Tc1/Type 1 cytokines in culture-positive lymph node tuberculosis

Cited by 8 publications

References 25 publications

Tuberculosis-induced aplastic crisis and atypical lymphocyte expansion in advanced myelodysplastic syndrome: A case report and review of literature

Tuberculosis-induced aplastic crisis and atypical lymphocyte expansion in advanced myelodysplastic syndrome: A case report and review of literature

Leukemic transformation during anti-tuberculosis treatment in aplastic anemia-paroxysmal nocturnal hemoglobinuria syndrome: A case report and review of literature

Safety and Immunogenicity of an In Vivo Muscle Electroporation Delivery System for DNA-hsp65 Tuberculosis Vaccine in Cynomolgus Monkeys

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