Jean-Marc Doisne | University of Cambridge (original) (raw)

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Papers by Jean-Marc Doisne

Research paper thumbnail of IL-12/15/18-preactivated NK cells suppress GvHD in a mouse model of mismatched hematopoietic cell transplantation

European journal of immunology, Jan 16, 2015

Mismatched hematopoietic cell transplants for treating leukemia are complicated by graft versus h... more Mismatched hematopoietic cell transplants for treating leukemia are complicated by graft versus host disease (GvHD). Here we show that adoptively transferred IL-12/15/18-preactivated NK cells suppress GvHD in a mouse model of fully mismatched hematopoietic cell transplantation. These IL-12/15/18-preactivated NK cells maintained Eomesodermin (Eomes) and T-bet expression upon transfer and, while there was no evidence of direct killing of donor T cells or host dendritic cells by the IL-12/15/18-preactivated NK cells, proliferation of donor T cells was inhibited. Strikingly, the graft versus leukemia effect mediated by donor T cells was retained, resulting in improved overall survival of mice that received lymphoma cells, donor allogeneic T cells and IL-12/15/18-preactivated NK cells. These results suggest that IL-12/15/18-preactivated NK cells may be useful in improving immunotherapy of mismatched hematopoietic cell transplantation. Compared with previously proposed protocols, our find...

Research paper thumbnail of Immunomodulation of Selective Naive T Cell Functions by p110δ Inactivation Improves the Outcome of Mismatched Cell Transplantation

Cell Reports, 2015

Highlights d Genetic p110d inactivation in donor naive T cells mitigates GvHD in mice d Pharmacol... more Highlights d Genetic p110d inactivation in donor naive T cells mitigates GvHD in mice d Pharmacological p110d inactivation in human T cells reduces alloreactivity

Research paper thumbnail of Impact of antiretroviral therapy and changes in virus load on human immunodeficiency virus (HIV)-specific T cell responses in primary HIV infection

The Journal of infectious diseases, 2003

Human immunodeficiency virus (HIV)-specific CD4(+) and CD8(+) T cell responses were evaluated pro... more Human immunodeficiency virus (HIV)-specific CD4(+) and CD8(+) T cell responses were evaluated prospectively in a large cohort of subjects with HIV primary infection via long-term follow-up examining different virological profiles related to different treatment interventions. No correlation was observed between baseline virus load and HIV-specific CD4(+) and CD8(+) T cell responses. Highly active antiretroviral therapy (HAART)-induced suppression of viremia was associated with an increase in CD4(+) T cell proliferative responses. The HIV-specific proliferative response also increased, at least in the first 18 months, in subjects with detectable viremia, either treated or untreated. The magnitude of the HIV-specific CD8(+) T cell response decreased with suppression of viremia. In subjects with detectable viremia, the breadth and magnitude of the HIV-specific CD8(+) T cell responses increased progressively. Finally, whether HAART was initiated before or after seroconversion had little ...

Research paper thumbnail of Impact of antiretroviral therapy and changes in virus load on human immunodeficiency virus (HIV)-specific T cell responses in primary HIV infection

The Journal of infectious diseases, Jan 1, 2003

Research paper thumbnail of CD8+ T cells specific for EBV, cytomegalovirus, and influenza virus are activated during primary HIV infection

Journal of immunology (Baltimore, Md. : 1950), Jan 1, 2004

Research paper thumbnail of Coordinated expression of Ig-like inhibitory MHC class I receptors and acquisition of cytotoxic function in human CD8+ T cells

Journal of immunology (Baltimore, Md. : 1950), Jan 1, 2004

Research paper thumbnail of The context of HLA-DR/CD18 complex in the plasma membrane governs HLA-DR-derived signals in activated monocytes

Molecular immunology, Jan 1, 2008

HLA-DR-derived signals in activated monocytes mediate both pro-inflammatory cytokine production a... more HLA-DR-derived signals in activated monocytes mediate both pro-inflammatory cytokine production and caspase-independent death, and have been postulated to play a role in inflammation and in its resolution, respectively. Herein, using the monocytic/macrophagic human cell line THP-1 primed with IFNγ (IFNγ-primed THP-1), we investigated how HLA-DR may integrate both signals. Our inhibition studies demonstrated that if cell death is dependent on PKCβ activation, the induction of TNFα gene expression relies on PTK activation, in particular the Src family of kinases, but both cell responses implicate the β2-integrin CD18. Accordingly, sequential immunoprecipitation experiments demonstrated that following engagement of HLA-DR on IFNγ-primed THP-1 cells, the HLA-DR/CD18 complex physically associates with PKCβ and with PTK. Pharmacological disruption of lipid rafts microdomains abolished the assembly of HLA-DR/CD18/PTK signaling complex, HLA-DR-mediated tyrosine activation, and the PTK-dependent TNFα expression in IFNγ-primed THP-1 cells. In contrast, HLA-DR/CD18/PKCβ complex was still formed and able to mediate cell death after cholesterol depletion of these cells. These results indicate that while the integrity of lipid rafts is necessary for the transduction of cytokine gene expression through the HLA-DR/CD18 complex, it is not necessary for the induction of the HLA-DR/CD18-dependent cell death. Thus, our study provides experimental evidence indicating the compartmentalization of HLA-DR/CD18 complex within or outside lipid rafts as a mechanism through which HLA-DR can integrate both PTK and PKCβ signals leading to activation and death, respectively, of activated monocytes. This might provide new insights into how MHC class II signaling may regulate inflammatory response.

Research paper thumbnail of Identification of a particular HIV-specific CD8+ T-cell subset with a CD27+ CD45RO-/RA+ phenotype and memory characteristics after initiation of HAART during acute primary HIV infection

Research paper thumbnail of iNKT cell development is orchestrated by different branches of TGF-beta signaling

The Journal of experimental medicine, Jan 1, 2009

Research paper thumbnail of Skin and peripheral lymph node invariant NKT cells are mainly retinoic acid receptor-related orphan receptor (gamma)t+ and respond preferentially under inflammatory conditions

Journal of immunology (Baltimore, Md. : 1950), Jan 1, 2009

Lymph nodes (LNs) have been long considered as comprising few invariant NKT (iNKT) cells, and the... more Lymph nodes (LNs) have been long considered as comprising few invariant NKT (iNKT) cells, and these cells have not been studied extensively. In this study, we unravel the existence of stable rather than transitional LN-resident NK1.1 ؊ iNKT cell populations. We found the one resident in peripheral LNs (PLNs) to comprise a major IL-17-producing population and to express the retinoic acid receptor-related orphan receptor ␥t (ROR␥t). These cells respond to their ligand ␣-galactosylceramide (␣-GalCer) in vivo by expanding dramatically in the presence of LPS, providing insight into how this rare population could have an impact in immune responses to infection. PLN-resident ROR␥t ؉ NK1.1 ؊ iNKT cells express concomitantly CCR6, the integrin ␣-chain ␣ E (CD103), and IL-1R type I (CD121a), indicating that they might play a role in inflamed epithelia. Accordingly, skin epithelia comprise a major ROR␥t ؉ CCR6 ؉ CD103 ؉ CD121a ؉ NK1.1 ؊ cell population, reflecting iNKT cell composition in PLNs. Importantly, both skin and draining PLN ROR␥t ؉ iNKT cells respond preferentially to inflammatory signals and independently of IL-6, indicating that they could play a nonredundant role during inflammation. Overall, our study indicates that ROR␥t ؉ iNKT cells could play a major role in the skin during immune responses to infection and autoimmunity.

Research paper thumbnail of Cutting edge: crucial role of IL-1 and IL-23 in the innate IL-17 response of peripheral lymph node NK1.1- invariant NKT cells to bacteria

Journal of immunology (Baltimore, Md. : 1950), Jan 1, 2011

Research paper thumbnail of Guardian of the genome turns on genes that alert natural killer cells

Cell cycle (Georgetown, Tex.), Jan 1, 2011

Cell Cycle News & Views. Guardian of the genome turns on genes that alert natural killer cell... more Cell Cycle News & Views. Guardian of the genome turns on genes that alert natural killer cells. Volume 10, Issue 22 November 15, 2011 Page 3822 http://dx.doi.org/10.4161/cc.10.22.18196Jean-Marc Doisne, Thomas Chin Che Tan and Francesco Colucci. ...

Research paper thumbnail of IL-12/15/18-preactivated NK cells suppress GvHD in a mouse model of mismatched hematopoietic cell transplantation

European journal of immunology, Jan 16, 2015

Mismatched hematopoietic cell transplants for treating leukemia are complicated by graft versus h... more Mismatched hematopoietic cell transplants for treating leukemia are complicated by graft versus host disease (GvHD). Here we show that adoptively transferred IL-12/15/18-preactivated NK cells suppress GvHD in a mouse model of fully mismatched hematopoietic cell transplantation. These IL-12/15/18-preactivated NK cells maintained Eomesodermin (Eomes) and T-bet expression upon transfer and, while there was no evidence of direct killing of donor T cells or host dendritic cells by the IL-12/15/18-preactivated NK cells, proliferation of donor T cells was inhibited. Strikingly, the graft versus leukemia effect mediated by donor T cells was retained, resulting in improved overall survival of mice that received lymphoma cells, donor allogeneic T cells and IL-12/15/18-preactivated NK cells. These results suggest that IL-12/15/18-preactivated NK cells may be useful in improving immunotherapy of mismatched hematopoietic cell transplantation. Compared with previously proposed protocols, our find...

Research paper thumbnail of Immunomodulation of Selective Naive T Cell Functions by p110δ Inactivation Improves the Outcome of Mismatched Cell Transplantation

Cell Reports, 2015

Highlights d Genetic p110d inactivation in donor naive T cells mitigates GvHD in mice d Pharmacol... more Highlights d Genetic p110d inactivation in donor naive T cells mitigates GvHD in mice d Pharmacological p110d inactivation in human T cells reduces alloreactivity

Research paper thumbnail of Impact of antiretroviral therapy and changes in virus load on human immunodeficiency virus (HIV)-specific T cell responses in primary HIV infection

The Journal of infectious diseases, 2003

Human immunodeficiency virus (HIV)-specific CD4(+) and CD8(+) T cell responses were evaluated pro... more Human immunodeficiency virus (HIV)-specific CD4(+) and CD8(+) T cell responses were evaluated prospectively in a large cohort of subjects with HIV primary infection via long-term follow-up examining different virological profiles related to different treatment interventions. No correlation was observed between baseline virus load and HIV-specific CD4(+) and CD8(+) T cell responses. Highly active antiretroviral therapy (HAART)-induced suppression of viremia was associated with an increase in CD4(+) T cell proliferative responses. The HIV-specific proliferative response also increased, at least in the first 18 months, in subjects with detectable viremia, either treated or untreated. The magnitude of the HIV-specific CD8(+) T cell response decreased with suppression of viremia. In subjects with detectable viremia, the breadth and magnitude of the HIV-specific CD8(+) T cell responses increased progressively. Finally, whether HAART was initiated before or after seroconversion had little ...

Research paper thumbnail of Impact of antiretroviral therapy and changes in virus load on human immunodeficiency virus (HIV)-specific T cell responses in primary HIV infection

The Journal of infectious diseases, Jan 1, 2003

Research paper thumbnail of CD8+ T cells specific for EBV, cytomegalovirus, and influenza virus are activated during primary HIV infection

Journal of immunology (Baltimore, Md. : 1950), Jan 1, 2004

Research paper thumbnail of Coordinated expression of Ig-like inhibitory MHC class I receptors and acquisition of cytotoxic function in human CD8+ T cells

Journal of immunology (Baltimore, Md. : 1950), Jan 1, 2004

Research paper thumbnail of The context of HLA-DR/CD18 complex in the plasma membrane governs HLA-DR-derived signals in activated monocytes

Molecular immunology, Jan 1, 2008

HLA-DR-derived signals in activated monocytes mediate both pro-inflammatory cytokine production a... more HLA-DR-derived signals in activated monocytes mediate both pro-inflammatory cytokine production and caspase-independent death, and have been postulated to play a role in inflammation and in its resolution, respectively. Herein, using the monocytic/macrophagic human cell line THP-1 primed with IFNγ (IFNγ-primed THP-1), we investigated how HLA-DR may integrate both signals. Our inhibition studies demonstrated that if cell death is dependent on PKCβ activation, the induction of TNFα gene expression relies on PTK activation, in particular the Src family of kinases, but both cell responses implicate the β2-integrin CD18. Accordingly, sequential immunoprecipitation experiments demonstrated that following engagement of HLA-DR on IFNγ-primed THP-1 cells, the HLA-DR/CD18 complex physically associates with PKCβ and with PTK. Pharmacological disruption of lipid rafts microdomains abolished the assembly of HLA-DR/CD18/PTK signaling complex, HLA-DR-mediated tyrosine activation, and the PTK-dependent TNFα expression in IFNγ-primed THP-1 cells. In contrast, HLA-DR/CD18/PKCβ complex was still formed and able to mediate cell death after cholesterol depletion of these cells. These results indicate that while the integrity of lipid rafts is necessary for the transduction of cytokine gene expression through the HLA-DR/CD18 complex, it is not necessary for the induction of the HLA-DR/CD18-dependent cell death. Thus, our study provides experimental evidence indicating the compartmentalization of HLA-DR/CD18 complex within or outside lipid rafts as a mechanism through which HLA-DR can integrate both PTK and PKCβ signals leading to activation and death, respectively, of activated monocytes. This might provide new insights into how MHC class II signaling may regulate inflammatory response.

Research paper thumbnail of Identification of a particular HIV-specific CD8+ T-cell subset with a CD27+ CD45RO-/RA+ phenotype and memory characteristics after initiation of HAART during acute primary HIV infection

Research paper thumbnail of iNKT cell development is orchestrated by different branches of TGF-beta signaling

The Journal of experimental medicine, Jan 1, 2009

Research paper thumbnail of Skin and peripheral lymph node invariant NKT cells are mainly retinoic acid receptor-related orphan receptor (gamma)t+ and respond preferentially under inflammatory conditions

Journal of immunology (Baltimore, Md. : 1950), Jan 1, 2009

Lymph nodes (LNs) have been long considered as comprising few invariant NKT (iNKT) cells, and the... more Lymph nodes (LNs) have been long considered as comprising few invariant NKT (iNKT) cells, and these cells have not been studied extensively. In this study, we unravel the existence of stable rather than transitional LN-resident NK1.1 ؊ iNKT cell populations. We found the one resident in peripheral LNs (PLNs) to comprise a major IL-17-producing population and to express the retinoic acid receptor-related orphan receptor ␥t (ROR␥t). These cells respond to their ligand ␣-galactosylceramide (␣-GalCer) in vivo by expanding dramatically in the presence of LPS, providing insight into how this rare population could have an impact in immune responses to infection. PLN-resident ROR␥t ؉ NK1.1 ؊ iNKT cells express concomitantly CCR6, the integrin ␣-chain ␣ E (CD103), and IL-1R type I (CD121a), indicating that they might play a role in inflamed epithelia. Accordingly, skin epithelia comprise a major ROR␥t ؉ CCR6 ؉ CD103 ؉ CD121a ؉ NK1.1 ؊ cell population, reflecting iNKT cell composition in PLNs. Importantly, both skin and draining PLN ROR␥t ؉ iNKT cells respond preferentially to inflammatory signals and independently of IL-6, indicating that they could play a nonredundant role during inflammation. Overall, our study indicates that ROR␥t ؉ iNKT cells could play a major role in the skin during immune responses to infection and autoimmunity.

Research paper thumbnail of Cutting edge: crucial role of IL-1 and IL-23 in the innate IL-17 response of peripheral lymph node NK1.1- invariant NKT cells to bacteria

Journal of immunology (Baltimore, Md. : 1950), Jan 1, 2011

Research paper thumbnail of Guardian of the genome turns on genes that alert natural killer cells

Cell cycle (Georgetown, Tex.), Jan 1, 2011

Cell Cycle News & Views. Guardian of the genome turns on genes that alert natural killer cell... more Cell Cycle News & Views. Guardian of the genome turns on genes that alert natural killer cells. Volume 10, Issue 22 November 15, 2011 Page 3822 http://dx.doi.org/10.4161/cc.10.22.18196Jean-Marc Doisne, Thomas Chin Che Tan and Francesco Colucci. ...