HIV gag‐specific immune response mediated by double negative (CD3+CD4−CD8−) T cells in HIV‐exposed seronegative individuals

Restrepo, Clara; Rallón, Norma; Romero, Jorge del; Rodríguez, Carmen; Sempere-Ortells, José M.; Vega, Elvira de la; Soriano, Vincent; Benito, José M.

doi:10.1002/jmv.23447

Cited by 11 publications

(7 citation statements)

References 27 publications

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“…26 The same phenomena is well known in HIV-exposed individuals; T cells reactive to HIV present in some individuals exist in the absence of HIV-specific antibodies. [27][28][29][30][31][32][33][34] Similar observations are also made in Hepatitis Cand B-exposed individuals. [35][36][37][38] It is not known why serology tests for some viruses including HCMV are negative in some virus-exposed individuals.…”

Section: E982391-4 Volume 4 Issue 2 Oncoimmunologysupporting

confidence: 55%

Discordant humoral and cellular immune responses toCytomegalovirus(CMV) in glioblastoma patients whose tumors are positive for CMV

et al. 2015

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Submit your article to this journal Background. Glioblastoma (GBM) is the most common malignant brain tumor in adults and is nearly always fatal. Emerging evidence suggests that human Cytomegalovirus (HCMV) is present in 90-100% of GBMs and that add-on antiviral treatment for HCMV show promise to improve survival.Methods. In a randomized, placebo-controlled trial of valganciclovir in 42 GBM patients, blood samples were collected for analyses of HCMV DNA, RNA, reactivity against HCMV peptides, IgG, and IgM at baseline and at 3, 12, and 24 weeks of treatment.Results. All 42 tumors were positive for HCMV protein. All patients examined had at least one blood sample positive for HCMV DNA, 63% were HCMV RNA positive, and 21% were IgM positive. However, 29% of GBM patients were IgG negative for HCMV. Five of these samples were positive in an enzyme-linked immunosorbent assay (ELISA) that used antigens derived from a clinical isolate. Blood T cells from 11 of 13 (85%) HCMV IgG-negative GBM patients reacted against HCMV peptides. Valganciclovir did not affect IgG titers, DNA, or RNA levels of the HCMV immediate early (HCMV IE) gene in blood.Conclusion. In GBM patients, HCMV activity is higher than in healthy controls and serology is a poor test to define previous or active HCMV infection in these patients.

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Section: E982391-4 Volume 4 Issue 2 Oncoimmunologysupporting

confidence: 55%

Discordant humoral and cellular immune responses toCytomegalovirus(CMV) in glioblastoma patients whose tumors are positive for CMV

et al. 2015

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“…A de novo heterozygous mutation c.1192_1196delAGCCC (chr14: 99641977-99641981, NM_138576.2) was identified in BCL11B of the patient, resulting in a frameshift mutation p.S398Qfs * 117 that could produce truncated proteins (Figures 2B,C). The messy tail of the mutant protein was (7,(9)(10)(11).…”

Section: Sequencing Resultsmentioning

confidence: 99%

Mutant BCL11B in a Patient With a Neurodevelopmental Disorder and T-Cell Abnormalities

Yang

Kang

Hou³

et al. 2020

Front. Pediatr.

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Background: BCL11B encodes B-cell lymphoma/leukemia 11B, a transcription factor that participates in the differentiation and migration of neurons and lymphocyte cells. De novo mutations of BCL11B have been associated with neurodevelopmental disorder and immunodeficiency, such as immunodeficiency 49 (IMD49) and intellectual developmental disorder with speech delay, dysmorphic facies, and T-cell abnormalities (IDDSFTA). However, the pathogenesis of the neurodevelopmental disorder and T-cell deficiency is still mysterious. The strategy to distinguish these two diseases in detail is also unclear. Methods: A patient with unique clinical features was identified. Multiple examinations were applied for evaluation. Whole-exome sequencing (WES) and Sanger sequencing were also performed for the identification of the disease-causing mutation. Results: We reported a 17-month-old girl with intellectual disability, speech impairment, and delay in motor development. She presented with mild dysmorphic facial features and weak functional movement. MRI indicated the abnormal myelination of the white matter. Immunological analysis showed normal levels of RTEs and γδT cells but a deficiency of naive T cells. Genetic sequencing identified a de novo heterozygous frameshift mutation c.1192_1196delAGCCC in BCL11B. Conclusions: An IDDSFTA patient of East Asian origin was reported. The unreported neurological display, immunophenotype, and a novel disease-causing mutation of the patient extended the spectrum of clinical features and genotypes of IDDSFTA.

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“…Bridgett Ryan-Payseur [ 24 ] demonstrated, in non-human primates, multi-effector-functional Vγ9Vδ2 T-cell responses against L. monocytogenes producing or coproducing Th1 and Th2 or Th17 cytokines, and direct lysis of L. monocytogenes-infected target cells. Restrepo et al [ 25 ] showed a higher expression of bi-functional γδ T-cell subsets coproducing IFNγ and MIP-1β in HIV-exposed seronegative individuals than in HIV-infected partners and healthy donors. However, our data could not be compared with these data, because these authors stimulated γδ T cells with HIV peptides and not with constitutive phosphoantigens.…”

Section: Discussionmentioning

confidence: 99%

Vγ9Vδ2 T-Cell Polyfunctionality Is Differently Modulated in HAART-Treated HIV Patients according to CD4 T-Cell Count

et al. 2015

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Alteration of γδ T-cell distribution and function in peripheral blood is among the earliest defects during HIV-infection. We asked whether the polyfunctional response could also be affected, and how this impairment could be associated to CD4 T-cell count. To this aim, we performed a cross-sectional study on HIV-infected individuals. In order to evaluate the polyfunctional-Vγ9Vδ2 T-cell response after phosphoantigen-stimulation, we assessed the cytokine/chemokine production and cytotoxicity by flow-cytometry in HAART-treated-HIV+ persons and healthy-donors. During HIV-infection Vγ9Vδ2-polyfunctional response quality is affected, since several Vγ9Vδ2 T-cell subsets resulted significantly lower in HIV+ patients in respect to healthy donors. Interestingly, we found a weak positive correlation between Vγ9Vδ2 T-cell-response and CD4 T-cell counts. By dividing the HIV+ patients according to CD4 T-cell count, we found that Low-CD4 patients expressed a lower number of two Vγ9Vδ2 T-cell subsets expressing MIP-1β in different combinations with other molecules (CD107a/IFNγ) in respect to High-CD4 individuals. Our results show that the Vγ9Vδ2 T-cell-response quality in Low-CD4 patients is specifically affected, suggesting a direct link between innate Vγ9Vδ2 T-cells and CD4 T-cell count. These findings suggest that Vγ9Vδ2 T-cell quality may be indirectly influenced by HAART therapy and could be included in a new therapeutical strategy which would perform an important role in fighting HIV infection.

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HIV gag‐specific immune response mediated by double negative (CD3⁺CD4⁻CD8⁻) T cells in HIV‐exposed seronegative individuals

Cited by 11 publications

References 27 publications

Discordant humoral and cellular immune responses toCytomegalovirus(CMV) in glioblastoma patients whose tumors are positive for CMV

Discordant humoral and cellular immune responses toCytomegalovirus(CMV) in glioblastoma patients whose tumors are positive for CMV

Mutant BCL11B in a Patient With a Neurodevelopmental Disorder and T-Cell Abnormalities

Vγ9Vδ2 T-Cell Polyfunctionality Is Differently Modulated in HAART-Treated HIV Patients according to CD4 T-Cell Count

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