scholarly journals Altered Clonogenic Capability and Stromal Cell Function Characterize Bone Marrow of HIV‐Infected Subjects with Low CD4+T Cell Counts Despite Viral Suppression during HAART

2008 ◽  
Vol 46 (12) ◽  
pp. 1902-1910 ◽  
Author(s):  
Antonella Isgrò ◽  
Wilma Leti ◽  
Wladimiro De Santis ◽  
Marco Marziali ◽  
Antonella Esposito ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
Stromal Cell ◽  
Viral Suppression ◽  
Cell Function ◽  
Cd4 T Cell ◽  
Cell Counts

scholarly journals Brain cancer induces systemic immunosuppression through release of non-steroid soluble mediators

Brain ◽  
2020 ◽  
Author(s):  
Katayoun Ayasoufi ◽  
Christian K Pfaller ◽  
Laura Evgin ◽  
Roman H Khadka ◽  
Zachariah P Tritz ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
T Cell ◽  
Brain Cancer ◽  
Cd4 T Cell ◽  
Complex Class ◽  
Thymic Involution ◽  
Cell Counts ◽  
Histocompatibility Complex ◽  
Hallmark Feature

Abstract Immunosuppression of unknown aetiology is a hallmark feature of glioblastoma and is characterized by decreased CD4 T-cell counts and downregulation of major histocompatibility complex class II expression on peripheral blood monocytes in patients. This immunosuppression is a critical barrier to the successful development of immunotherapies for glioblastoma. We recapitulated the immunosuppression observed in glioblastoma patients in the C57BL/6 mouse and investigated the aetiology of low CD4 T-cell counts. We determined that thymic involution was a hallmark feature of immunosuppression in three distinct models of brain cancer, including mice harbouring GL261 glioma, B16 melanoma, and in a spontaneous model of diffuse intrinsic pontine glioma. In addition to thymic involution, we determined that tumour growth in the brain induced significant splenic involution, reductions in peripheral T cells, reduced MHC II expression on blood leucocytes, and a modest increase in bone marrow resident CD4 T cells. Using parabiosis we report that thymic involution, declines in peripheral T-cell counts, and reduced major histocompatibility complex class II expression levels were mediated through circulating blood-derived factors. Conversely, T-cell sequestration in the bone marrow was not governed through circulating factors. Serum isolated from glioma-bearing mice potently inhibited proliferation and functions of T cells both in vitro and in vivo. Interestingly, the factor responsible for immunosuppression in serum is non-steroidal and of high molecular weight. Through further analysis of neurological disease models, we determined that the immunosuppression was not unique to cancer itself, but rather occurs in response to brain injury. Non-cancerous acute neurological insults also induced significant thymic involution and rendered serum immunosuppressive. Both thymic involution and serum-derived immunosuppression were reversible upon clearance of brain insults. These findings demonstrate that brain cancers cause multifaceted immunosuppression and pinpoint circulating factors as a target of intervention to restore immunity.

scholarly journals HIV Patients Developing Primary CNS Lymphoma Lack EBV-Specific CD4+ T Cell Function Irrespective of Absolute CD4+ T Cell Counts

PLoS Medicine ◽  
2007 ◽  
Vol 4 (3) ◽  
pp. e96 ◽  
Author(s):  
Olivier Gasser ◽  
Florian K Bihl ◽  
Marcel Wolbers ◽  
Elisabetta Loggi ◽  
Ingrid Steffen ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Function ◽  
Primary Cns Lymphoma ◽  
Cd4 T Cell ◽  
Cns Lymphoma ◽  
Hiv Patients ◽  
Cell Counts ◽  
T Cell Function

scholarly journals Severe and multifaceted systemic immunosuppression caused by experimental cancers of the central nervous system requires release of non-steroid soluble mediators

2020 ◽  
Author(s):  
K Ayasoufi ◽  
CK Pfaller ◽  
L Evgin ◽  
RH Khadka ◽  
ZP Tritz ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
T Cell ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Cd4 T Cell ◽  
Unknown Etiology ◽  
Thymic Involution ◽  
Cell Counts ◽  
Hallmark Feature

AbstractImmunosuppression of unknown etiology is a hallmark feature of glioblastoma (GBM) and is characterized by decreased CD4 T cell counts and down regulation of MHC class II expression on peripheral blood monocytes in patients. This immunosuppression is a critical barrier to the successful development of immunotherapies for GBM. We recapitulated the immunosuppression observed in GBM patients in the C57BL/6 mouse and investigated the etiology of low CD4 T cell counts. We determined that thymic involution was a hallmark feature of immunosuppression in three distinct models of CNS cancer, including mice harboring GL261 glioma, B16 melanoma, and in a spontaneous model of Diffuse Intrinsic Pontine Glioma (DIPG). In addition to thymic involution, we determined that tumor growth in the brain induced significant splenic involution, reductions in peripheral T cells, reduced MHC class II expression on hematopoietic cells, and a modest increase in bone marrow resident CD4 T cells with a naïve phenotype. Using parabiosis we report that thymic involution, declines in peripheral T cell counts, and reduced MHC class II expression levels were mediated through circulating blood-derived factors. Conversely, T cell sequestration in the bone marrow was not governed through circulating factors. Serum isolated from glioma-bearing mice potently inhibited proliferation and functions of T cells both in vitro and in vivo. Interestingly, the factor responsible for immunosuppression in serum is nonsteroidal and of high molecular weight. Through further analysis of neurological disease models, we determined that the aforementioned immunosuppression was not unique to cancer itself, but rather occurs in response to CNS injury. Noncancerous acute neurological insults also induced significant thymic involution and rendered serum immunosuppressive. Both thymic involution and serum-derived immunosuppression were reversible upon clearance of brain insults. These findings demonstrate that CNS cancers cause multifaceted immunosuppression and pinpoint circulating factors as a target of intervention to restore immunity.Short SummaryCNS cancers and other brain-injuries suppress immunity through release of non-steroid soluble factors that disrupt immune homeostasis and dampen responses of the peripheral immune system.Graphical Abstract

Neutralizing antibodies are positively associated with CD4+ T-cell counts and T-cell function in long-term AIDS-free infection

AIDS ◽  
1998 ◽  
Vol 12 (13) ◽  
pp. 1591-1600 ◽  
Author(s):  
Patrizia Carotenuto ◽  
Dennis Looij ◽  
Lian Keldermans ◽  
Frank de Wolf ◽  
Jaap Goudsmit
Keyword(s):  
T Cell ◽  
Neutralizing Antibodies ◽  
Cell Function ◽  
Cd4 T Cell ◽  
Cell Counts ◽  
T Cell Function

scholarly journals A link between IL-23 and anti-CD4 autoantibody production in antiretroviral-treated HIV-infected individuals

2021 ◽  
Author(s):  
Zhenwu Luo ◽  
Min Li ◽  
Fuli Mi ◽  
Zhefeng Meng ◽  
Guoqiang Du ◽  
...  
Keyword(s):  
T Cell ◽  
Antibody Production ◽  
Viral Suppression ◽  
Cd4 T Cell ◽  
Hiv Disease ◽  
Cell Recovery ◽  
Autoantibody Production ◽  
Cell Counts

Potential mechanisms of poor CD4+ T cell reconstitution after viral suppression with antiretroviral therapy (ART) in HIV disease have been extensively investigated. We recently discovered that anti-CD4 autoantibody plays a role in impaired CD4+ T cell recovery from ART in HIV-infected individuals with viral suppression, which accounts for a mechanism specific for CD4+ T cell depletion. However, the mechanism of pathologic anti-CD4 autoantibody production in treated HIV disease remains unknown. Here we report that seasonal influenza vaccination induced IgG anti-CD4 autoantibodies, predominant IgG3 subclass, in some viral-suppressed ART-treated HIV+ subjects. To explore the mechanism of anti-CD4 antibody production in this population, we performed and analyzed gene profiles in isolated B cells using a gene microarray and plasma 32 cytokines. Notably, both gene expression and multiple cytokine analyses showed pre-vaccination plasma level of IL-23 was the key cytokine linked to IgG anti-CD4 antibody production in response to immunization in vivo. Exogenous rIL-23 increased autoreactive IgG binding on CD4+ T cells from HIV+ subjects in vitro. Results from this study may reveal a role of IL-23 in anti-CD4 autoantibody production in treated HIV. IMPORTANCE In our published studies, we determine that pathological anti-CD4 IgGs from immunologic non-responders on virally-suppressive ART (CD4 cell counts < 350 cells/μL) mediated CD4+ T cell death via antibody-mediated cytotoxicity (ADCC), which play a role in poor CD4+ T cell recovery from ART. Up to 25% of HIV-infected individuals are non-responders and demonstrate increased morbidity and mortality. However, the mechanism of anti-CD4 autoantibody production in treated HIV remains unknown. In this study, we report that IL-23 may be the key cytokine to promote anti-CD4 autoantibody production after immunization in ART-treated HIV-infected individuals.

scholarly journals IMMU-25. SEVERE AND MULTIFACETED SYSTEMIC IMMUNOSUPPRESSION CAUSED BY EXPERIMENTAL CANCERS OF THE CENTRAL NERVOUS SYSTEM REQUIRES RELEASE OF NON-STEROID SOLUBLE MEDIATORS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii110-ii110
Author(s):  
Katayoun Ayasoufi ◽  
Christian Pfaller ◽  
Laura Evgin ◽  
Roman Khadka ◽  
Zachariah Tritz ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
T Cell ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Cd4 T Cell ◽  
Unknown Etiology ◽  
Thymic Involution ◽  
Cell Counts ◽  
Hallmark Feature

Abstract Immunosuppression of unknown etiology is a hallmark feature of glioblastoma (GBM) and is characterized by decreased CD4 T cell counts and down regulation of MHC class II expression on peripheral blood monocytes in patients. This immunosuppression is a critical barrier to the successful development of immunotherapies for GBM. We recapitulated the immunosuppression observed in GBM patients in the C57BL/6 mouse and investigated the etiology of low CD4 T cell counts. We determined that thymic involution was a hallmark feature of immunosuppression in three distinct models of CNS cancer, including mice harboring GL261 glioma, B16 melanoma, and in a spontaneous model of Diffuse Intrinsic Pontine Glioma (DIPG). In addition to thymic involution, we determined that tumor growth in the brain induced significant splenic involution, reductions in peripheral T cells, reduced MHC class II expression on hematopoietic cells, and a modest increase in bone marrow resident CD4 T cells with a naïve phenotype. Using parabiosis we report that thymic involution, declines in peripheral T cell counts, and reduced MHC class II expression levels were mediated through circulating blood-derived factors. Conversely, T cell sequestration in the bone marrow was not governed through circulating factors. Serum isolated from glioma-bearing mice potently inhibited proliferation and functions of T cells both in vitro and in vivo. Interestingly, the factor responsible for immunosuppression in serum is nonsteroidal and of high molecular weight. Through further analysis of neurological disease models, we determined that the aforementioned immunosuppression was not unique to cancer itself, but rather occurs in response to CNS injury. Noncancerous acute neurological insults also induced significant thymic involution and rendered serum immunosuppressive. Both thymic involution and serum-derived immunosuppression were reversible upon clearance of brain insults. These findings demonstrate that CNS cancers cause multifaceted immunosuppression and pinpoint circulating factors as a target of intervention to restore immunity.

scholarly journals Eomesodermin regulate decidual CD4+T cell function during human early pregnancy

2021 ◽  
pp. 103290
Author(s):  
Lanting Chen ◽  
Mengdie Li ◽  
Fengrun Sun ◽  
Jinfeng Qian ◽  
Meirong Du ◽  
...  
Keyword(s):  
T Cell ◽  
Early Pregnancy ◽  
Cell Function ◽  
Cd4 T Cell ◽  
T Cell Function
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