Sequestration of T Lymphocytes to Body Fluids in Tuberculosis: Reversal of Anergy following Chemotherapy

Dieli, Francesco; Friscia, Giuseppe; Sano, Caterina Di; Iványi, Juraj; Singh, Mahavir; Spallek, Ralf; Sireci, Guido; Titone, Lucina; Salerno, Alfredo

doi:10.1086/314852

Cited by 51 publications

(52 citation statements)

References 12 publications

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“…T-cell clones were used for the proliferation assay at least 3 days after the last IL-2 addition. This cloning procedure, using PHA and allogeneic stimulation, induces the expansion of virtually all CD4 T cells and does not introduce any bias in the T-cell repertoire [1,8].…”

Section: Methodsmentioning

confidence: 99%

“…We have reported that CD4 T cells recognizing a vast array of Mycobacterium tuberculosis epitopes are sequestered at the site of disease in anergic TB patients, but appear in peripheral blood after chemotherapy [1]. Previous studies showed that chemotherapy leads to a rise in antibody levels to several antigens [2].…”

Section: Introductionmentioning

confidence: 96%

“…Immune parameters may be useful: (1) to con®rm diagnosis and avoid the continuation of unnecessary treatment; (2) to identify noncompliance with therapy; (3) as prognostic markers of therapeutic success; or (4) for the identi®cation of immunomodulators, which could be bene®cial to the ef®cacy of therapy.…”

Section: Introductionmentioning

confidence: 99%

“…In contrast to previous studies which mostly used bulk-lymphocyte cultures, we determined here the quantitative representation and the cytokine-production pro®les of cloned CD4 T cells in the peripheral blood and in the disease-affected body¯uids. We also investigated if the cytokine pro®le is associated with the recognition of different peptides of the 16-kDa a-crystallin antigen, as we have previously reported that postchemotherapy changes in T cell proliferative response in TB patients are particularly striking for T cells recognizing the 16-kDa a-crystallin [1].…”

Section: Introductionmentioning

confidence: 99%

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Change of Th0 to Th1 Cell‐Cytokine Profile Following Tuberculosis Chemotherapy

et al. 2000

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T cells mediate protection against tuberculosis, but little is known about their role during chemotherapy of patients with active disease. Here we examined the cytokine profile of CD4 T cells before and after four months of chemotherapy in six initial skin test anergic cases. Purified protein derivative (PPD) and 16‐kDa antigen‐reactive CD4 T‐cell clones prior to therapy resided mostly in disease‐associated body fluids and were of the Th0 (interferon (IFN)‐γ + interleukin (IL)‐4) secreting profile. In contrast, the majority of postchemotherapy CD4 T‐cell clones originated from blood and were of the IFN‐γ secreting Th1 type. However, the recognition of several peptides derived from the 16‐kDa antigen was not significantly different between the Th1 and Th0 clones. We conclude that chemotherapy shifts CD4 T cells from the affected body fluids to the blood circulation, accompanied by a change from Th0 to Th1 cytokine profile.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Change of Th0 to Th1 Cell‐Cytokine Profile Following Tuberculosis Chemotherapy

et al. 2000

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“…It is possible that some of the relative deficit in IFNc expression [89] and lymphoproliferation in the peripheral blood of tuberculosis patients is due to sequestration of the antigen-recognising cells in the lymph-nodes [98] or site of disease [99]. However this cannot fully explain the massive rise in expression of Type 2 cytokines [89].…”

Section: Type 2 Responses In Human Tuberculosismentioning

confidence: 99%

M. tuberculosis: immunology and vaccination

2001

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Tuberculosis is increasing. Current treatment regimens require at least 6 months, because latent or stationary phase organisms are difficult to kill. Such regimens do not achieve full compliance, and "directly observed therapy short course" (DOTS) is having less impact than expected. This worrying situation is aggravated by coinfection with human immunodeficiency virus (HIV), and by the increase in drug-resistant strains.We need new insights that lead to more rapid therapies and immunotherapies, and more reliable vaccines.Recent insights have come from: understanding of the relationship between Mycobacterium tuberculosis and macrophages; the multiple T cell types that recognise mycobacterial peptides, lipids and glycolipids; the critical role of interferon-c (IFNc) and interleukin-12 (IL-12) in human mycobacterial infection revealed by genetically defective children; quantitation of the presence and importance of Th2 lymphocyte activation in human tuberculosis; the role of local conversion of inactive cortisone to active cortisol in the lesions; the recognition that some effective prophylactic vaccines also work as immumotherapeutics whereas others do not. In the longer term the recent sequencing of the M. tuberculosis genome will lead to further advances.In the short term, effective immunotherapy remains the most accessible breakthrough in the management of tuberculosis. The types of practical advance that will result from sequencing the genome are discussed speculatively, but cannot yet be predicted with certainty.

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CD69flow cytometry to complement interferon‐γrelease assay for active tuberculosis

Kim

Han

Kim

et al. 2022

Cytometry Part B Clinical

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Background The interferon‐γ (IFN‐γ) release assay (IGRA) is widely used to diagnose tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb). However, indeterminate IGRA results due to “high Nil” or “low PHA” responses limit its clinical utility. We developed a novel assay using CD69 flow cytometry (FC) to complement IGRA. Methods CD69 FC measures the surface CD69 expression on T cells prior to centrifugation to harvest the plasma for IGRA. T cell responses against Mtb antigen 1 (Ag1) or Ag2 were measured using three‐color FC (CD3, CD4, and CD69) in TB (n = 140) and non‐TB groups (n = 117). The cutoff values of Δ%CD69bright cells (stimulated minus unstimulated) for CD4+ and CD4− T cells were established based on healthy individuals (n = 63). The assay performances of CD69 FC and IGRA were compared. Results In subjects with determinate IGRA results (“positive” or “negative”; n = 216), the diagnostic accuracies of CD69 FC (90.3%) and IGRA (87.0%) were not significantly different (p = 0.31). For indeterminate IGRA results (n = 40), CD69 FC attained a diagnostic accuracy of 92.5%. The CD4+/CD4− ratio within CD69bright T cells measured by CD69 FC was significantly higher (p < 0.05) in the active TB group (6.39 ± 132.05; n = 72) than in other CD69 FC‐positive subjects (2.84 ± 15.36; n = 63) (p < 0.05), whereas CD8 responses expected by IGRA (difference of IFN‐γ levels between Mtb Ag tubes) did not differ significantly (0.00 ± 9.18 and 0.00 ± 4.25, respectively, IU/ml; p = 0.58). Conclusions We demonstrated the potential of CD69 FC as a simple, rapid assay for clarifying indeterminate IGRA results and identifying active TB. With further improvements, CD69 FC may complement the IGRA to enhance TB risk stratification in the routine diagnostic workup.

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Sequestration of T Lymphocytes to Body Fluids in Tuberculosis: Reversal of Anergy following Chemotherapy

Cited by 51 publications

References 12 publications

Change of Th0 to Th1 Cell‐Cytokine Profile Following Tuberculosis Chemotherapy

Change of Th0 to Th1 Cell‐Cytokine Profile Following Tuberculosis Chemotherapy

M. tuberculosis: immunology and vaccination

CD69flow cytometry to complement interferon‐γrelease assay for active tuberculosis

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