Circulating CD4+CD8+ T lymphocytes in patients with Kawasaki disease

Hirao, Jun; Sugita, Kenichi

doi:10.1046/j.1365-2249.1998.00480.x

Cited by 25 publications

(15 citation statements)

References 24 publications

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“…The vast majority of DP-T cells arising in myeloma-infiltrated bones converted CD8ab heterodimer (expressed on SP-CD8 + T N prior to adoptive transfer into myeloma-bearing mice) to CD8aa homodimer. This phenotype makes the DP-T cells present in myelomainfiltrated bones similar to DP-T cells found in Hodgkin's lymphoma (29), Kawasaki's disease (33), and inflammatory bowel disease (34), but discriminates them from DP-T cells found in breast cancer and melanoma that express the CDab heterodimer (16,17). Functional studies on tumor-associated DP-T cells expressing CD8ab heterodimer or CD8aa homodimer are still lacking, precluding understanding of the physiological relevance of each particular cell subset.…”

Section: Discussionmentioning

confidence: 79%

Myeloma-Induced Alloreactive T Cells Arising in Myeloma-Infiltrated Bones Include Double-Positive CD8+CD4+ T Cells: Evidence from Myeloma-Bearing Mouse Model

Freeman

Lam

Petcu

et al. 2011

The Journal of Immunology

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The graft-versus-myeloma (GVM) effect represents a powerful form of immune attack exerted by alloreactive T cells against multiple myeloma cells, which leads to clinical responses in multiple myeloma transplant recipients. Whether myeloma cells are themselves able to induce alloreactive T cells capable of the GVM effect is not defined. Using adoptive transfer of T naive cells into myeloma-bearing mice (established by transplantation of human RPMI8226-TGL myeloma cells into CD122+ cell-depleted NOD/SCID hosts), we found that myeloma cells induced alloreactive T cells that suppressed myeloma growth and prolonged survival of T cell recipients. Myeloma-induced alloreactive T cells arising in the myeloma-infiltrated bones exerted cytotoxic activity against resident myeloma cells, but limited activity against control myeloma cells obtained from myeloma-bearing mice that did not receive T naive cells. These myeloma-induced alloreactive T cells were derived through multiple CD8+ T cell divisions and enriched in double-positive (DP) T cells coexpressing the CD8αα and CD4 coreceptors. MHC class I expression on myeloma cells and contact with T cells were required for CD8+ T cell divisions and DP-T cell development. DP-T cells present in myeloma-infiltrated bones contained a higher proportion of cells expressing cytotoxic mediators IFN-γ and/or perforin compared with single-positive CD8+ T cells, acquired the capacity to degranulate as measured by CD107 expression, and contributed to an elevated perforin level seen in the myeloma-infiltrated bones. These observations suggest that myeloma-induced alloreactive T cells arising in myeloma-infiltrated bones are enriched with DP-T cells equipped with cytotoxic effector functions that are likely to be involved in the GVM effect.

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Section: Discussionmentioning

confidence: 79%

Myeloma-Induced Alloreactive T Cells Arising in Myeloma-Infiltrated Bones Include Double-Positive CD8+CD4+ T Cells: Evidence from Myeloma-Bearing Mouse Model

Freeman

Lam

Petcu

et al. 2011

The Journal of Immunology

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“…12,31 The DP T cells that we observed in breast tumor samples were predominantly CD4 low CD8 high and CD8ab. This profile differentiates them from the CD4 high CD8 low DP T cells described in Hodgkin lymphoma, 31 Kawasaki disease 32 and in intestinal inflammatory bowel disease 33 and from intestinal DP T cells because these cells express the CD8aa homodimer.…”

Section: Discussionmentioning

confidence: 87%

Increased frequency of nonconventional double positive CD4CD8 αβ T cells in human breast pleural effusions

Desfrançois

Derré

Corvaisier

et al. 2009

Intl Journal of Cancer

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Breast cancer remains a leading cause of cancer-related death within the female population. Immunotherapy is expected to provide additional therapeutic benefits but has met so far limited success. This may be due in part to the poor understanding of immune responses to breast cancer. Although CD4 1 and CD8 1 T lymphocytes infiltrate these tumors, the phenotype and functions of these cells remain ill defined. This study was designed to investigate further about these questions, taking advantage of multiparameter flow cytometry on lymphocytes derived from peripheral blood, solid tumors, metastatic lymph nodes and pleural effusions samples of patients with breast cancer. Results showed that, in addition to conventional CD4 1 and CD8 1 ab T cells, individual tumors and most pleural effusions contained significant fractions of unconventional double positive (DP) CD4 1 CD8 1 ab T cells. These DP T cells displayed the phenotype and cytotoxic potential of effector/memory activated CD8 1 T cells but differed essentially from these cells by a high production of IL-5 and IL-13. The increased frequency of DP T cells in advanced breast cancer and their high lytic potential and original cytokine profile suggest that this T-cell subset may play a specific role in the regulation of immune responses to human breast cancer. ' 2009 UICC

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“…They have also been found in patients with Kawasaki syndrome and Hodgkin lymphoma (35,36). Following transplantation, only a single study has described them in organ biopsies, but not formally demonstrated coexpression of CD4 and CD8 (37).…”

Section: Discussionmentioning

confidence: 99%

Isolation of Human CD4/CD8 Double-Positive, Graft-Versus-Host Disease–Protective, Minor Histocompatibility Antigen–Specific Regulatory T Cells and of a Novel HLA-DR7–Restricted HY-Specific CD4 Clone

Eljaafari

Yuruker

Ferrand

et al. 2013

The Journal of Immunology

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Minor histocompatibility (H) Ags are classically described as self-peptides derived from intracellular proteins that are expressed at the cell surface by MHC class I and class II molecules and that induce T cell alloresponses. We have isolated three different T cell populations from a skin biopsy of a patient suffering from acute graft-versus-host disease following sex-mismatched HLA-identical bone marrow transplantation. The first population was: 1) CD4+/CD8+ double-positive; 2) specific for an HLA class I–restricted autosomal Ag; 3) expressed a Tr1 profile with high levels of IL-10, but low IL-2 and IFN-γ; and 4) exerted regulatory function in the presence of recipient APCs. The second was CD8 positive, specific for an HLA class I–restricted autosomally encoded minor H Ag, but was only weakly cytotoxic. The third was CD4 single positive, specific for an HLA-DR7–restricted HY epitope and exerted both proliferative and cytotoxic functions. Identification of the peptide recognized by these latter cells revealed a new human HY epitope, TGKIINFIKFDTGNL, encoded by RPS4Y and restricted by HLA-DR7. In this paper, we show human CD4/CD8 double-positive, acute graft-versus-host disease–protective, minor H Ag–specific regulatory T cells and identify a novel HLA-DR7/ HY T cell epitope, encoded by RPS4Y, a potential new therapeutic target.

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Circulating CD4+CD8+ T lymphocytes in patients with Kawasaki disease

Cited by 25 publications

References 24 publications

Myeloma-Induced Alloreactive T Cells Arising in Myeloma-Infiltrated Bones Include Double-Positive CD8+CD4+ T Cells: Evidence from Myeloma-Bearing Mouse Model

Myeloma-Induced Alloreactive T Cells Arising in Myeloma-Infiltrated Bones Include Double-Positive CD8+CD4+ T Cells: Evidence from Myeloma-Bearing Mouse Model

Increased frequency of nonconventional double positive CD4CD8 αβ T cells in human breast pleural effusions

Isolation of Human CD4/CD8 Double-Positive, Graft-Versus-Host Disease–Protective, Minor Histocompatibility Antigen–Specific Regulatory T Cells and of a Novel HLA-DR7–Restricted HY-Specific CD4 Clone

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