Increased Production of Inflammatory Cytokines in Cultured CD4+ Cells from Patients with HTLV-I-Associated Myelopathy.

Nishiura, Yoshihiro; Nakamura, Tatsufumi; Ichinose, Katsuhiro; Shirabe, Susumu; Tsujino, Akira; Goto, Hiroyuki; Furuya, Takafumi; Nagataki, Shigenobu

doi:10.1620/tjem.179.227

Cited by 35 publications

(31 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We conclude that the high frequency of HTLV-I-specific CD4 ϩ T cells was associated with the disease HAM/TSP. This conclusion is corroborated by evidence from several sources: 1) the predominant T cell in early HAM/TSP lesions is the CD4 ϩ T cell (8); 2) HTLV-I-infected CD4 ϩ T cells spontaneously produce proinflammatory cytokines (11,12,18); 3) activated CD4…”

Section: Figure 3 Detection Of Cmv-specific Cd4mentioning

confidence: 70%

“…In particular, the spontaneous proliferation (34 -36) and spontaneous cytokine production (12,15,18) associated with HTLV-I infection complicate assays of both T cell proliferation and cytokine detection. To overcome these problems, we recently established 6-h ELISPOT and intracellular cytokine staining assays and detected significant frequencies of Env and Tax-specific CD4 ϩ T cells in infected subjects (19).…”

Section: Discussionmentioning

confidence: 99%

“…3) CD4 ϩ T cells carry most of the HTLV-I proviral load burden in vivo (9, 10) and a high proviral load is associated with the development of HAM/ TSP. 4) HTLV-I-infected CD4 ϩ T cells spontaneously secrete proinflammatory, neurotoxic cytokines such as IFN-␥, TNF-␣, and GM-CSF (11,12) which are found in high levels in the cerebrospinal fluid and spinal cord lesions of HAM/TSP (13)(14)(15).…”

Section: ) Cd4mentioning

confidence: 99%

“…Further longitudinal studies are required in patients with active disease to ascertain whether the circulating HTLV-I-specific CD4 ϩ T cell frequency is indeed correlated with disease activity. A recent report suggested that HLA-A2/Tax [11][12][13][14][15][16][17][18][19] specific CTLs are correlated with disease severity (32). At present, the best marker of disease activity is thought to be the level of neopterin in the cerebrospinal fluid (47,51).…”

Section: Figure 3 Detection Of Cmv-specific Cd4mentioning

confidence: 99%

See 3 more Smart Citations

Human T Cell Lymphotropic Virus Type I (HTLV-I)-Specific CD4+ T Cells: Immunodominance Hierarchy and Preferential Infection with HTLV-I

Goon¹,

Igakura²,

Hanon³

et al. 2004

The Journal of Immunology

View full text Add to dashboard Cite

CD4+ T cells predominate in early lesions in the CNS in the inflammatory disease human lymphotropic T cell virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP), but the pathogenesis of the disease remains unclear and the HTLV-I-specific CD4+ T cell response has been little studied. We quantified the IFN-γ-producing HTLV-I-specific CD4+ T cells, in patients with HAM/TSP and in asymptomatic carriers with high proviral load, to test two hypotheses: that HAM/TSP patients and asymptomatic HTLV-I carriers with a similar proviral load differ in the immunodominance hierarchy or the total frequency of specific CD4+ T cells, and that HTLV-I-specific CD4+ T cells are preferentially infected with HTLV-I. The strongest CD4+ T cell response in both HAM/TSP patients and asymptomatic carriers was specific to Env. This contrasts with the immunodominance of Tax in the HTLV-I-specific CD8+ T cell response. The median frequency of HTLV-I-specific IFN-γ+ CD4+ T cells was 25-fold greater in patients with HAM/TSP (p = 0.0023, Mann-Whitney) than in asymptomatic HTLV-I carriers with a similar proviral load. Furthermore, the frequency of CD4+ T cells infected with HTLV-I (expressing Tax protein) was significantly greater (p = 0.0152, Mann-Whitney) among HTLV-I-specific cells than CMV-specific cells. These data were confirmed by quantitative PCR for HTLV-I DNA. We conclude that the high frequency of specific CD4+ T cells was associated with the disease HAM/TSP, and did not simply reflect the higher proviral load that is usually found in HAM/TSP patients. Finally, we conclude that HTLV-I-specific CD4+ T cells are preferentially infected with HTLV-I.

show abstract

Section: Figure 3 Detection Of Cmv-specific Cd4mentioning

confidence: 70%

Section: Discussionmentioning

confidence: 99%

Section: ) Cd4mentioning

confidence: 99%

Section: Figure 3 Detection Of Cmv-specific Cd4mentioning

confidence: 99%

See 2 more Smart Citations

Human T Cell Lymphotropic Virus Type I (HTLV-I)-Specific CD4+ T Cells: Immunodominance Hierarchy and Preferential Infection with HTLV-I

Goon¹,

Igakura²,

Hanon³

et al. 2004

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…Of particular interest, HAM/TSP patients display an activated inflammatory immune response associated with a decreased suppressive capacity in Treg cells (Nishiura et al 1996). In contrast, it has been demonstrated that the immunocompromised state seen in ATLL patients may be a result of clonal expansion of a Treg precursor, suppressing anti-tumor immunity ).…”

Section: Discussionmentioning

confidence: 99%

The Role of HTLV-1 in Alteration of Immune Regulation Through Regulatory T Cell Dysfunction and Exosomal Manipulation

Anderson

View full text Add to dashboard Cite

Phenotypic and functional changes in gamma delta T lymphocytes from HTLV-1 carriers

Albuquerque

Granato

Castro

et al. 2019

Journal of Leukocyte Biology

View full text Add to dashboard Cite

Human T‐cell lymphotropic virus type‐1 (HTLV‐1) is the etiologic agent of HTLV‐1‐associated myelopathy/tropical spastic paraparesis (HAM/TSP), which is a chronic inflammatory disease that leads to gradual loss of motor movement as a result of the death of spinal cord cells through immune mediated mechanisms. The risk to develop HAM/TSP disease positively correlates with the magnitude of HTLV‐1 proviral load. Gamma‐delta T lymphocytes have been recognized as important players in a variety of infectious diseases. Therefore, we have investigated interactions between HTLV‐1 infection and γδ T lymphocytes during HAM/TSP. Similar frequencies of total γδ T lymphocytes and their Vγ9δ2+ and Vγ9δ2neg subpopulations were observed in HAM/TSP patients. However, T lymphocytes obtained from HTLV‐1 carriers displayed significantly higher rates of spontaneous proliferation and NKp30 expression when compared to cells from uninfected donors. In addition, an important decrease in the frequency of granzyme B+ γδ T lymphocytes (approximately 50%) was observed in HAM/TSP patients. Higher proportion of IFN‐γ+ γδ T lymphocytes was found in HTLV‐1‐infected patients, which positively correlated with the HTLV‐1 proviral load in peripheral blood mononuclear cells. Collectively, our data indicates that HTLV‐1 infection leads to phenotypic and functional changes in the population of γδ T lymphocyte population, suggesting that HTLV‐1 infection modulates functions associated to these cells, which might be involved in controlling the infection or in the development of HTLV‐1‐associated diseases.

show abstract

Increased Production of Inflammatory Cytokines in Cultured CD4+ Cells from Patients with HTLV-I-Associated Myelopathy.

Cited by 35 publications

References 16 publications

Human T Cell Lymphotropic Virus Type I (HTLV-I)-Specific CD4+ T Cells: Immunodominance Hierarchy and Preferential Infection with HTLV-I

Human T Cell Lymphotropic Virus Type I (HTLV-I)-Specific CD4+ T Cells: Immunodominance Hierarchy and Preferential Infection with HTLV-I

The Role of HTLV-1 in Alteration of Immune Regulation Through Regulatory T Cell Dysfunction and Exosomal Manipulation

Phenotypic and functional changes in gamma delta T lymphocytes from HTLV-1 carriers

Contact Info

Product

Resources

About