In vivo Expression of Human T-lymphotropic Virus Type 1 Basic Leucine-Zipper Protein Generates Specific CD8+ and CD4+ T-Lymphocyte Responses that Correlate with Clinical Outcome

Hilburn, Silva; Rowan, Aileen; Demontis, Maria-Antonietta; MacNamara, Aidan; Asquith, Becca; Bangham, Charles R. M.; Taylor, Graham P.

doi:10.1093/infdis/jiq078

Cited by 66 publications

(80 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This observation supports our hypothesis. An earlier study (36) reported that HBZ-specific T cell responses were detected in some patients with HTLV-1-associated myelopathy (HAM). Unlike ATL, HAM can occur in individuals infected with HTLV-1 by any route of transmission, such as sexual intercourse (37).…”

Section: Discussionmentioning

confidence: 99%

HTLV-1 bZIP Factor–Specific CD4 T Cell Responses in Adult T Cell Leukemia/Lymphoma Patients after Allogeneic Hematopoietic Stem Cell Transplantation

Narita

Ishida

Awata

et al. 2014

The Journal of Immunology

View full text Add to dashboard Cite

We document human T lymphotropic virus type 1 (HTLV-1) bZIP factor (HBZ)-specific CD4 T cell responses in an adult T cell leukemia/lymphoma (ATL) patient after allogeneic hematopoietic stem cell transplantation (HCT) and identified a novel HLA-DRB1*15:01–restricted HBZ-derived naturally presented minimum epitope sequence, RRRAEKKAADVA (HBZ114–125). This peptide was also presented on HLA-DRB1*15:02, recognized by CD4 T cells. Notably, HBZ-specific CD4 T cell responses were only observed in ATL patients after allogeneic HCT (4 of 9 patients) and not in nontransplanted ATL patients (0 of 10 patients) or in asymptomatic HTLV-1 carriers (0 of 10 carriers). In addition, in one acute-type patient, HBZ-specific CD4 T cell responses were absent in complete remission before HCT, but they became detectable after allogeneic HCT. We surmise that HTLV-1 transmission from mothers to infants through breast milk in early life induces tolerance to HBZ and results in insufficient HBZ-specific T cell responses in HTLV-1 asymptomatic carriers or ATL patients. In contrast, after allogeneic HCT, the reconstituted immune system from donor-derived cells can recognize virus protein HBZ as foreign, and HBZ-specific immune responses are provoked that contribute to the graft-versus-HTLV-1 effect.

show abstract

Section: Discussionmentioning

confidence: 99%

HTLV-1 bZIP Factor–Specific CD4 T Cell Responses in Adult T Cell Leukemia/Lymphoma Patients after Allogeneic Hematopoietic Stem Cell Transplantation

Narita

Ishida

Awata

et al. 2014

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…At the same way as for Tax, HBZ-specific CD8+ T cell response appears to be important to maintain low proviral load and asymptomatic status of carriers (Hilburn et al, 2011).…”

Section: Ham/tspmentioning

confidence: 99%

Human T-Lymphotropic Viruses (HTLV)

Martins¹,

Andrade²,

Nédir³

et al. 2012

Blood Transfusion in Clinical Practice

View full text Add to dashboard Cite

“…The ability of an individual's HLA-alleles to bind peptides from HBZ has been shown to correlate inversely with proviral load and risk of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) [11]. Despite its significant protective potential, the binding affinity of HBZ peptides to HLA class I molecules was found to be significantly weaker than that of peptides from Tax, and the frequency of HBZ-specific CD8 + T cells in peripheral blood was extremely low [11,12], although the IL-2 secreting HBZ-specific CD8 + T cells were more frequently detected in individuals with a viral load of below 1% of PBMCs [12]. In addition, HBZ protein is present at levels barely detectable by western blot; inefficient polyadenylation and transport of mRNA from the nucleus are thought to be responsible for this low expression [4,[13][14][15].…”

Section: Htlv-1-infected Autologous Cd4mentioning

confidence: 99%

Cytotoxic T lymphocyte lysis of HTLV-1 infected cells is limited by weak HBZ protein expression, but non-specifically enhanced on induction of Tax expression

Rowan¹,

Suemori²,

Fujiwara³

et al. 2014

Retrovirology

View full text Add to dashboard Cite

Background: Immunogenetic evidence indicates that cytotoxic T lymphocytes (CTLs) specific for the weak CTL antigen HBZ limit HTLV-1 proviral load in vivo, whereas there is no clear relationship between the proviral load and the frequency of CTLs specific for the immunodominant antigen Tax. In vivo, circulating HTLV-1-infected cells express HBZ mRNA in contrast, Tax expression is typically low or undetectable. To elucidate the virus-suppressing potential of CTLs targeting HBZ, we compared the ability of HBZ-and Tax-specific CTLs to lyse naturally-infected cells, by co-incubating HBZ-and Tax-specific CTL clones with primary CD4 + T cells from HLA-matched HTLV-1-infected donors. We quantified lysis of infected cells, and tested whether specific virus-induced host cell surface molecules determine the susceptibility of infected cells to CTL-mediated lysis.

show abstract

In vivo Expression of Human T-lymphotropic Virus Type 1 Basic Leucine-Zipper Protein Generates Specific CD8+ and CD4+ T-Lymphocyte Responses that Correlate with Clinical Outcome

Abstract: HBZ protein is expressed in vivo in patients with HAM and in ACs. Our results are consistent with the idea that the T cell response to HBZ plays an important part in restricting HTLV-1 viral load.

Cited by 66 publications

References 36 publications

HTLV-1 bZIP Factor–Specific CD4 T Cell Responses in Adult T Cell Leukemia/Lymphoma Patients after Allogeneic Hematopoietic Stem Cell Transplantation

HTLV-1 bZIP Factor–Specific CD4 T Cell Responses in Adult T Cell Leukemia/Lymphoma Patients after Allogeneic Hematopoietic Stem Cell Transplantation

Human T-Lymphotropic Viruses (HTLV)

Cytotoxic T lymphocyte lysis of HTLV-1 infected cells is limited by weak HBZ protein expression, but non-specifically enhanced on induction of Tax expression

Contact Info

Product

Resources

About