scholarly journals Sex differences in autoimmunity could be associated with altered regulatory T cell phenotype and lipoprotein metabolism

2019 ◽  
Author(s):  
George A Robinson ◽  
Kirsty E Waddington ◽  
Marsilio Adriani ◽  
Anna Radziszewska ◽  
Hannah Peckham ◽  
...  
Keyword(s):  
Sex Differences ◽  
T Cell ◽  
Regulatory T Cell ◽  
Immune Cell ◽  
Pubertal Development ◽  
Cell Subset ◽  
Cell Phenotype ◽  
Healthy Adolescent ◽  
Treg Frequency ◽  
And Function

ABSTRACTMale and female immune responses are known to differ resulting in an increased prevalence of autoimmunity in women. Here sex differences in T-cell subset frequency and function during adolescence were examined in healthy donors and patients with the autoimmune disease juvenile (J)SLE; onset of JSLE commonly occurs during puberty suggesting a strong hormonal influence. Healthy adolescent males had increased regulatory T-cell (Treg) frequency, and increased Treg suppressive capacity and IL-4 production compared to healthy adolescent females. The T-helper 2-like profile in male Tregs was associated with increased expression of GATA3 which correlated significantly with elevated Treg plasma membrane glycosphingolipid expression. Differential Treg phenotype was associated with unique serum metabolomic profiles in males compared to female adolescents. Notably, very low density lipoprotein (VLDL) metabolomic signatures correlated positively with activated Tregs in males but with resting Tregs in females. Consistently, only VLDL isolated from male serum was able to induce increased Treg IL-4 production and glycosphingolipid expression following in cultured cells. Remarkably, gender differences in Treg frequency, phenotype and function and serum metabolomic profiles were lost in adolescents with JSLE. This work provides evidence that a combination of pubertal development, immune cell defects and dyslipidemia may contribute to JSLE pathogenesis.

CD4+CD25+ Marrow Infiltrating Lymphocytes in Myeloma Patients Display an Activated Phenotype and Lack Suppressive Function.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1741-1741
Author(s):  
Kimberly A. Noonan ◽  
Stephanie Mgebroff ◽  
Paolo Serafini ◽  
Kristen Meckel ◽  
Mark Bonyhadi ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Population ◽  
Regulatory T Cell ◽  
Cell Phenotype ◽  
Autologous Tumor ◽  
Activation Markers ◽  
Tumor Specificity ◽  
And Function ◽  
Infiltrating Lymphocytes

Abstract We have previously shown that marrow infiltrating lymphocytes (MILs) from myeloma patients proliferate upon stimulation with anti-CD3/CD28 beads more efficiently and exhibit greater specificity to autologous tumor than their peripheral blood lymphocyte (PBL) counterparts. In attempting to dissect the mechanisms responsible for greater tumor specificity of MILs, we examined the frequency and function of the putative CD4+/CD25+ regulatory T cells (Tregs) in both compartments. Phenotypic and functional differences in the CD4+/CD25+ populations were examined in MILs and PBLs from 12 multiple myeloma patients and 3 normal donors. CD4+/CD25+ cells were stained for the suppressive marker: FoxP3; or the activation markers: CD40L, CD71 (transferrin receptor). CD4+/CD25+ MILs of myeloma patients are CD25lo, FoxP3lo and predominantly express activation markers. They expand more readily upon anti-CD3/CD28 stimulation, produce high amounts of the Th1 cytokines: IFNγ and IL-2, and low amounts of IL-10. Importantly, they fail to suppress the tumor specific T cell proliferation. These findings are all consistent with an activated T cell phenotype. In contrast, CD4+/CD25+ cells from PBLs of myeloma patients are CD25hi, FoxP3+, primarily produce IL-10 and IL-4 and markedly suppress T cell expansion in a tumor specific assay, suggestive of a regulatory T cell phenotype. Although MILs possess a lower number of FoxP3+ cells as compared to PBLs, the higher MFI may indicate the presence of a small yet highly regulatory T cell population. Interestingly, MILs from normal donors possess a more regulatory phenotype then their myeloma counterparts as determined by high FoxP3 and low CD40L and CD71 expression as well as reduced expansion upon activation. Taken together, these data underscore major differences in the immuno-inhibitory pathways present in blood as compared to marrow. Notably, MILs of myeloma patients demonstrate a paucity of Tregs. These differences may explain the disparities seen in the tumor-specificity of T cells from these two compartments. The ability to expand a T cell population with fewer endogenous Tregs and heightened tumor-specificity may have significant implications for the implementation of adoptive immunotherapy. %CD25 (MFI) %FoxP3 (MFI) %CD40L %CD71 Fold Expansion Ability to Suppress Myeloma CD4/CD25 MILs 4.7 (29.6) 2.2 (2932.1) 88.8 90.1 12.2 − CD4/CD25 PBLs 19.1 (115.2) 52.3 (163.7) 15.7 19.6 2.5 +++++ Normal CD4/CD25 MILs 14.0 (56.8) 70.1 (82.7) 37.3 6.4 3.3 +++ CD4/CD25 PBLs 24.0 (19.4) 30.9 (261.8) 12.1 4.2 4.0 ++

scholarly journals Regulatory T cell phenotype and function 4 years after GAD-alum treatment in children with type 1 diabetes

2013 ◽  
Vol 172 (3) ◽  
pp. 394-402 ◽  
Author(s):  
M. Pihl ◽  
L. Åkerman ◽  
S. Axelsson ◽  
M. Chéramy ◽  
M. Hjorth ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
T Cell ◽  
Regulatory T Cell ◽  
Cell Phenotype ◽  
Alum Treatment ◽  
And Function

Resting and Restimulation after Cryopreservation Restores Regulatory T Cell Phenotype and Function.

2014 ◽  
Vol 98 ◽  
pp. 677-678
Author(s):  
J. Weiner ◽  
R. Duran-Struuck ◽  
J. Zitsman ◽  
M. Sykes ◽  
A. Griesemer
Keyword(s):  
T Cell ◽  
Regulatory T Cell ◽  
Cell Phenotype ◽  
And Function

scholarly journals Impacts of HIV infection on Vγ2Vδ2 T cell phenotype and function: a mechanism for reduced tumor immunity in AIDS

2008 ◽  
Vol 84 (2) ◽  
pp. 371-379 ◽  
Author(s):  
Jean-Saville Cummings ◽  
Cristiana Cairo ◽  
Cheryl Armstrong ◽  
Charles E. Davis ◽  
C. David Pauza
Keyword(s):  
T Cell ◽  
Hiv Infection ◽  
Tumor Immunity ◽  
Cell Phenotype ◽  
And Function

scholarly journals Pathophysiology of acute respiratory syndrome coronavirus 2 infection: a systematic literature review to inform EULAR points to consider

RMD Open ◽  
2021 ◽  
Vol 7 (1) ◽  
pp. e001549 ◽  
Author(s):  
Aurélie Najm ◽  
Alessia Alunno ◽  
Xavier Mariette ◽  
Benjamin Terrier ◽  
Gabriele De Marco ◽  
...  
Keyword(s):  
Literature Review ◽  
Systematic Literature Review ◽  
Immune Cell ◽  
Severe Disease ◽  
Cell Phenotype ◽  
Loss Of Function ◽  
Humoral And Cellular Immunity ◽  
Host Immune Responses ◽  
Disease Spectrum ◽  
And Function

BackgroundThe SARS-CoV-2 pandemic is a global health problem. Beside the specific pathogenic effect of SARS-CoV-2, incompletely understood deleterious and aberrant host immune responses play critical roles in severe disease. Our objective was to summarise the available information on the pathophysiology of COVID-19.MethodsTwo reviewers independently identified eligible studies according to the following PICO framework: P (population): patients with SARS-CoV-2 infection; I (intervention): any intervention/no intervention; C (comparator): any comparator; O (outcome) any clinical or serological outcome including but not limited to immune cell phenotype and function and serum cytokine concentration.ResultsOf the 55 496 records yielded, 84 articles were eligible for inclusion according to question-specific research criteria. Proinflammatory cytokine expression, including interleukin-6 (IL-6), was increased, especially in severe COVID-19, although not as high as other states with severe systemic inflammation. The myeloid and lymphoid compartments were differentially affected by SARS-CoV-2 infection depending on disease phenotype. Failure to maintain high interferon (IFN) levels was characteristic of severe forms of COVID-19 and could be related to loss-of-function mutations in the IFN pathway and/or the presence of anti-IFN antibodies. Antibody response to SARS-CoV-2 infection showed a high variability across individuals and disease spectrum. Multiparametric algorithms showed variable diagnostic performances in predicting survival, hospitalisation, disease progression or severity, and mortality.ConclusionsSARS-CoV-2 infection affects both humoral and cellular immunity depending on both disease severity and individual parameters. This systematic literature review informed the EULAR ‘points to consider’ on COVID-19 pathophysiology and immunomodulatory therapies.

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