scholarly journals Early Thymectomy Is Associated With Long-Term Impairment of the Immune System: A Systematic Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Nara Vasconcelos Cavalcanti ◽  
Patrícia Palmeira ◽  
Marcelo Biscegli Jatene ◽  
Mayra de Barros Dorna ◽  
Magda Carneiro-Sampaio
Keyword(s):  
Systematic Review ◽  
T Cells ◽  
Immune System ◽  
T Cell ◽  
Heart Diseases ◽  
Subsequent Development ◽  
Treg Cells ◽  
Ki 67 ◽  
T Cell Subpopulations

Background and AimsCongenital heart diseases (CHDs) are diagnosed in approximately 9 in 1,000 newborns, and early cardiac corrective surgery often requires partial or complete thymectomy. As the long-term effect of early thymectomy on the subsequent development of the immune system in humans has not been completely elucidated, the present study aimed to evaluate the effects of thymus removal on the functional capacity of the immune system after different periods.MethodsA systematic review of the literature was performed using MEDLINE, EMBASE, LILACS and Scopus. The inclusion criteria were original studies that analyzed any component of the immune system in patients with CHD who had undergone thymectomy during cardiac surgery in the first years of life. The results were evaluated for the quality of evidence.ResultsTwenty-three studies were selected and showed that patients who underwent a thymectomy in the first years of life tended to exhibit important alterations in the T cell compartment, such as fewer total T cells, CD4+, CD8+, naïve and CD31+ T cells, lower TRECs, decreased diversity of the TCR repertoire and higher peripheral proliferation (increased Ki-67 expression) than controls. However, the numbers of memory T cells and Treg cells differed across the selected studies.ConclusionsEarly thymectomy, either partial or complete, may be associated with a reduction in many T cell subpopulations and TCR diversity, and these alterations may persist during long-term follow-up. Alternative solutions should be studied, either in the operative technique with partial preservation of the thymus or through the autograft of fragments of the gland.Systematic Review RegistrationProspero [157188].

scholarly journals Analysis of the Long-Term Impact on Cellular Immunity in COVID-19-Recovered Individuals Reveals a Profound NKT Cell Impairment

mBio ◽  
2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Jia Liu ◽  
Xuecheng Yang ◽  
Hua Wang ◽  
Ziwei Li ◽  
Hui Deng ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
T Cell ◽  
Cellular Immunity ◽  
Cd8 T Cells ◽  
Nkt Cell ◽  
Cellular Immune System ◽  
Long Term Impact ◽  
Cellular Immune

ABSTRACT The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affected over 120 million people and killed over 2.7 million individuals by March 2021. While acute and intermediate interactions between SARS-CoV-2 and the immune system have been studied extensively, long-term impacts on the cellular immune system remain to be analyzed. Here, we comprehensively characterized immunological changes in peripheral blood mononuclear cells in 49 COVID-19-convalescent individuals (CI) in comparison to 27 matched SARS-CoV-2-unexposed individuals (UI). Despite recovery from the disease for more than 2 months, CI showed significant decreases in frequencies of invariant NKT and NKT-like cells compared to UI. Concomitant with the decrease in NKT-like cells, an increase in the percentage of annexin V and 7-aminoactinomycin D (7-AAD) double-positive NKT-like cells was detected, suggesting that the reduction in NKT-like cells results from cell death months after recovery. Significant increases in regulatory T cell frequencies and TIM-3 expression on CD4 and CD8 T cells were also observed in CI, while the cytotoxic potential of T cells and NKT-like cells, defined by granzyme B (GzmB) expression, was significantly diminished. However, both CD4 and CD8 T cells of CI showed increased Ki67 expression and were fully able to proliferate and produce effector cytokines upon T cell receptor (TCR) stimulation. Collectively, we provide a comprehensive characterization of immune signatures in patients recovering from SARS-CoV-2 infection, suggesting that the cellular immune system of COVID-19 patients is still under a sustained influence even months after the recovery from disease. IMPORTANCE Wuhan was the very first city hit by SARS-CoV-2. Accordingly, the patients who experienced the longest phase of convalescence following COVID-19 reside here. This enabled us to investigate the “immunological scar” left by SARS-CoV-2 on cellular immunity after recovery from the disease. In this study, we characterized the long-term impact of SARS-CoV-2 infection on the immune system and provide a comprehensive picture of cellular immunity of a convalescent COVID-19 patient cohort with the longest recovery time. We revealed that the cellular immune system of COVID-19 patients is still under a sustained influence even months after the recovery from disease; in particular, a profound NKT cell impairment was found in the convalescent phase of COVID-19.

scholarly journals Defining the Immune Checkpoint Landscape in Patients (pts) with Acute Myeloid Leukemia (AML)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2900-2900 ◽  
Author(s):  
Naval Daver ◽  
Sreyashi Basu ◽  
Guillermo Garcia-Manero ◽  
Jorge E. Cortes ◽  
Farhad Ravandi ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Research Funding ◽  
Treg Cells ◽  
Immune Checkpoints ◽  
Live Cells ◽  
Median Frequency ◽  
Healthy Controls ◽  
T Cell Subpopulations

Abstract Introduction: Immune checkpoint therapy has been successful in many solid tumors andHodgkins lymphoma.The expression and clinical implications of immune checkpoints in the tumor microenvironment in patients (pts) with AML remain poorly defined.Identification and targeting of immune checkpoints in AMLwill guide the rational selection of specific antibodies for clinical trials. Methods:Between March, 2015 and April 2016 we performed17-colormulti-parameter flow-cytometry (MFC) on bone marrows (BM) aspirate from 74 pts with AML (36 untreated AML, 38 relapsed AML). We evaluated expression of immune receptors (inhibitory receptors: PD1, CTLA4, LAG3, TIM3, and activating receptors GITR, OX40, 41BB, ICOS) on T-cell subsets: CD4 T effector cells [Teff]: CD3+CD4+CD127lo/+Foxp3, CD4 T regulatory cells [Treg]: CD3+CD4+CD127-Foxp3+, and CD8 T cells. AML blasts were assessed for both immune receptors (as above), and ligands (4-1BBL, B7-1, B7-2, ICOSL, PDL-1, PDL-2, OX40L).Eight healthy human BMs were used as control. These analyses were performed on freshly collected BM aspirate by the M. D. Anderson Cancer Center Immunotherapy Platform. Results: A total of 74 pts were evaluated. Our analyses show that T-cell populations are preserved in BM of untreated and relapsed AML patients. In untreated AML BM, median frequency of live CD3+, CD4+, and CD8+ T cells were 16.5%, 10.4%, and 5.1% respectively. In relapsed AML BM, median frequency of live CD3+, CD4+, and CD8+ T cells were 19.2%, 9.5%, and 4.5% respectively. The expression of the8 costimreceptors and 7 ligands varied significantly between individual AML pts. On analysis of all markers PD-1 and OX40 emerged as potential checkpoint receptors of importance in AML.The baseline expression of OX40 and PD-1 on the CD8, Teff, and Treg cells are shown in Figure 1. All T cell subpopulations had significantly higher PD1 expression in relapsed AML (P<0.006) and untreated AML (P<0.05) compared to healthy controls. There were no significant differences in PD1 expression between relapsed and untreated AML. OX40 expression was significantly higher on all T cell subpopulations in relapsed AML pts (P<0.006) and specifically on Teff cells in untreated AML (P<0.006) when compared to healthy controls. Moreover, Treg cells in relapsed AML pts expressed significantly higher OX40 compared to untreated AML.The expression of costimulatory receptors and ligands differed significantly between BM and PB for the same time-point in the same pt (PB data not shown here). We compared the T-cell repertoire and checkpoint receptor/ligand expression to baseline clinical characteristics (age, cytogenetics, therapy-related status) and outcomes. Pts with untreated AML with adverse karyotype had a higher expression of PDL2 on AML blasts (P=0.07) in the BM. Pts with untreated AML who responded to induction therapy had a trend to higher Teff live cells (P=0.2), and lower OX40 on CD8 cells (P=0.04) in the BM. In relapsed AML higher T-eff live cells (P=0.04) and higher OX40 expression on CD8 (P=0.009) in BM were associated with improved survival. Conclusions: Total T-cell and T-cell subset populations are preserved in the BM of pts with untreated and relapsed AML and may be manipulated by checkpoint antibodies. Clinically targetable checkpoint receptors, specifically PD1 and OX40 are overexpressed in the BM of pts with AML and may be manipulated to unleash T-cells. PD1 and OX40 expression in new (N=34) and relapsed AML (N=38), and healthy controls (N=8) PD1 and OX40 expression in new (N=34) and relapsed AML (N=38), and healthy controls (N=8) Disclosures Daver: BMS: Research Funding; Kiromic: Research Funding; Karyopharm: Honoraria, Research Funding; Pfizer: Consultancy, Research Funding; Sunesis: Consultancy, Research Funding; Otsuka: Consultancy, Honoraria; Ariad: Research Funding. Cortes:ARIAD: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Teva: Research Funding. Konopleva:Calithera: Research Funding; Cellectis: Research Funding.

scholarly journals Venetoclax imparts distinct cell death sensitivity and adaptivity patterns in T cells

2021 ◽  
Vol 12 (11) ◽  
Author(s):  
Lindsey M. Ludwig ◽  
Katrina M. Hawley ◽  
David B. Banks ◽  
Anika T. Thomas-Toth ◽  
Bruce R. Blazar ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Death ◽  
Immune System ◽  
T Cell ◽  
T Cell Subsets ◽  
Treatment Modalities ◽  
Short Term ◽  
Bh3 Mimetics ◽  
Post Transplant

AbstractBH3 mimetics are increasingly used as anti-cancer therapeutics either alone or in conjunction with other chemotherapies. However, mounting evidence has also demonstrated that BH3 mimetics modulate varied amounts of apoptotic signaling in healthy immune populations. In order to maximize their clinical potential, it will be essential to understand how BH3 mimetics affect discrete immune populations and to determine how BH3 mimetic pressure causes immune system adaptation. Here we focus on the BCL-2 specific inhibitor venetoclax (ABT-199) and its effects following short-term and long-term BCL-2 blockade on T cell subsets. Seven day “short-term” ex vivo and in vivo BCL-2 inhibition led to divergent cell death sensitivity patterns in CD8+ T cells, CD4+ T cells, and Tregs resulting in shifting of global T cell populations towards a more memory T cell state with increased expression of BCL-2, BCL-XL, and MCL-1. However, twenty-eight day “long-term” BCL-2 blockade following T cell-depleted bone marrow transplantation did not lead to changes in the global T cell landscape. Despite the lack of changes in T cell proportions, animals treated with venetoclax developed CD8+ and CD4+ T cells with high levels of BCL-2 and were more resistant to apoptotic stimuli following expansion post-transplant. Further, we demonstrate through RNA profiling that T cells adapt while under BCL-2 blockade post-transplant and develop a more activated genotype. Taken together, these data emphasize the importance of evaluating how BH3 mimetics affect the immune system in different treatment modalities and disease contexts and suggest that venetoclax should be further explored as an immunomodulatory compound.

scholarly journals The Regulatory Effects of mTOR Complexes in the Differentiation and Function of CD4+ T Cell Subsets

2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Peng Wang ◽  
Qian Zhang ◽  
Liang Tan ◽  
Yanan Xu ◽  
Xubiao Xie ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Metabolism ◽  
Adaptive Immune System ◽  
Treg Cells ◽  
T Cell Subsets ◽  
Regulatory Effects ◽  
Phosphoinositide 3 Kinase ◽  
T Cell Subpopulations ◽  
And Function

T cells are an important part of the adaptive immune system and play critical roles in the elimination of various pathogens. T cells could differentiate into distinct cellular subsets under different extracellular signals and then play different roles in maintaining host homeostasis and defense. The mechanistic target of rapamycin (mTOR) is a conserved intracellular serine/threonine kinase which belongs to the phosphoinositide 3-kinase- (PI3K-) related kinase family. The mTOR signaling pathway is closely involved in a variety of cell biological processes, including cell growth and cell metabolism, by senses and integrates various environmental cues. Recent studies showed that mTOR including mTORC1 and mTORC2 is closely involved in the development of T cell subpopulations such as Th1, Th2, Th9, Th17, follicular helper T cells (Tfh), and Treg cells through distinctive pathways. We herein mainly focused on the recent progress in understanding the roles of mTOR in regulating the development and differentiation of CD4+ T cell subsets.

scholarly journals Depletion of CD25+ T cells from hematopoietic stem cell grafts increases posttransplantation vaccine-induced immunity to neuroblastoma

Blood ◽  
2011 ◽  
Vol 117 (25) ◽  
pp. 6952-6962 ◽  
Author(s):  
Weiqing Jing ◽  
Xiaocai Yan ◽  
William H. D. Hallett ◽  
Jill A. Gershan ◽  
Bryon D. Johnson
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Antitumor Immunity ◽  
Treg Cells ◽  
T Cell Memory ◽  
Hematopoietic Stem ◽  
Hsc Transplantation

Abstract A multifaceted immunotherapeutic strategy that includes hematopoietic stem cell (HSC) transplantation, T-cell adoptive transfer, and tumor vaccination can effectively eliminate established neuroblastoma tumors in mice. In vivo depletion of CD4+ T cells in HSC transplantation recipients results in increased antitumor immunity when adoptively transferred T cells are presensitized, but development of T-cell memory is severely compromised. Because increased percentages of regulatory T (Treg) cells are seen in HSC transplantation recipients, here we hypothesized that the inhibitory effect of CD4+ T cells is primarily because of the presence of expanded Treg cells. Remarkably, adoptive transfer of presensitized CD25-depleted T cells increased tumor vaccine efficacy. The enhanced antitumor effect achieved by ex vivo depletion of CD25+ Treg cells was similar to that achieved by in vivo depletion of all CD4+ T cells. Depletion of CD25+ Treg cells resulted in elevated frequencies of tumor-reactive CD8 and CD4+ T cells and increased CD8-to-Treg cell ratios inside tumor masses. All mice given presensitized CD25-depleted T cells survived a tumor rechallenge, indicating the development of long-term CD8+ T-cell memory to tumor antigens. These observations should aid in the future design of immunotherapeutic approaches that promote the generation of both acute and long-term antitumor immunity.

scholarly journals Effects of Telbivudine Treatment on the Circulating CD4+T-Cell Subpopulations in Chronic Hepatitis B Patients

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Yanhua Zheng ◽  
Zemin Huang ◽  
Xianhua Chen ◽  
Yi Tian ◽  
Jun Tang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Hepatitis B ◽  
Antiviral Agents ◽  
Adaptive Immune Response ◽  
Treg Cells ◽  
T Cell Subsets ◽  
Th2 Cells ◽  
Th1 Cell ◽  
T Cell Subpopulations

CD4+T cells serve as master regulators of the adaptive immune response to HBV. However, CD4+T-cell subsets are heterogeneous, and it remains unknown how the antiviral agents affect the different CD4+T cell subtypes. To this end, the expressions of signature transcription factors and cytokines of CD4+T-cell subtypes were examined in hepatitis B patients before and after treatment with telbivudine. Results showed that, upon the rapid HBV copy decrease induced by telbivudine treatment, the frequencies and related cytokines of Th17 and Treg cells were dramatically decreased, while those for Th2 cells were dramatically increased. No obvious changes were observed in Th1 cell frequencies; although, IFN-γexpression was upregulated in response to telbivudine treatment, suggesting another cell source of IFN-γin CHB patients. Statistical analyses indicated that Th17 and Tr1 (a Treg subtype) cells were the most sensitive subpopulations of the peripheral blood CD4+T cells to telbivudine treatment over 52 weeks. Thus, Th17 and Tr1 cells may represent a suitable and effective predictor of responsiveness during telbivudine therapy. These findings not only improve our understanding of hepatitis pathogenesis but also can aid in future development of appropriate therapeutic strategies to control viral hepatitis.

scholarly journals Sialyl Lewis x (CD15s) identifies highly differentiated and most suppressive FOXP3high regulatory T cells in humans

2015 ◽  
Vol 112 (23) ◽  
pp. 7225-7230 ◽  
Author(s):  
Makoto Miyara ◽  
Driss Chader ◽  
Edouard Sage ◽  
Daisuke Sugiyama ◽  
Hiroyoshi Nishikawa ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Cell Receptor ◽  
Treg Cells ◽  
Sialyl Lewis X ◽  
Lewis X ◽  
Sialyl Lewis ◽  
T Cell Subpopulations

CD4+ regulatory T (Treg) cells expressing CD25 and the transcription factor forkhead box P3 (FOXP3) are indispensable for immunological self-tolerance and homeostasis. FOXP3+CD25+CD4+ T cells in humans, however, are heterogeneous in function and differentiation status, including suppressive or nonsuppressive cells as well as resting or activated Treg cells. We have searched for cell surface markers specific for suppression-competent Treg cells by using a panel of currently available monoclonal antibodies reactive with human T cells. We found that CD15s (sialyl Lewis x) was highly specific for activated, terminally differentiated, and most suppressive FOXP3high effector Treg (eTreg) cells and able to differentiate them in various clinical settings from nonsuppressive FOXP3+ T cells secreting inflammatory cytokines. For example, CD15s+FOXP3+ eTreg cells were increased in sarcoidosis, whereas it was nonsuppressive CD15s−FOXP3+ T cells that were expanded in lupus flares. FOXP3+ cells induced from conventional CD4+ T cells by T-cell receptor stimulation hardly expressed CD15s. CD15s+CD4+ T-cell depletion was sufficient to evoke and enhance in vitro immune responses against tumor or viral antigens. Collectively, we have identified CD15s as a biomarker instrumental in both phenotypic and functional analysis of FOXP3+CD4+ T-cell subpopulations in health and disease. It allows specific targeting of eTreg cells, rather than whole FOXP3+CD4+ T cells, in controlling immune responses.

scholarly journals IMMUNOLOGICAL MEMORY: THE ROLE OF REGULATORY CELLS (TREGS)

2018 ◽  
Vol 20 (5) ◽  
pp. 613-620
Author(s):  
E. K. Oleinik ◽  
A. V. Churov ◽  
V. M. Oleinik
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune System ◽  
T Cell ◽  
Structural Organization ◽  
Memory T Cells ◽  
Treg Cells ◽  
T Cell Memory ◽  
Peripheral Tissues

Memory T cells are necessary for development of the immune response and represent one of the most numerous population of human T lymphocytes. On the contrary, suppressive regulatory T cells (Tregs) may terminate the immune response and help to maintain tolerance to self-antigens. These important groups of cells are consisting of different subpopulations and retaining throughout life. However, today there is yet no clear understanding of how the relations between these two groups of cells are formed. In this work we consider possible ways of development and maintenance of CD4+ T cell memory and role of Tregs in these processes. Mechanisms of a differentiation of memory T cells, Tregs and recently described memory Tregs are discussed. The functional and genetic characteristics of these cells are compared. Division of cells according to the functional profile allows drawing parallels between memory T cells and Tregs. These two groups are consisted of central circulating populations (Tc), effector which can migrate toward specific tissues (Te) and tissue-resident cells (Tr), which are staying in peripheral tissues. The similar structural organization of Tregs and memory T cells, existence of transitional forms of tissue-resident Treg subpopulations with properties of memory cells assumes existence of close interrelation between these groups of lymphocytes. The conversion of CD4+ memory T cells into FoxP3-expressing Tregs is one of possible mechanisms of communication between these two groups. The memory Treg-cells with T cell and memory Treg-cell properties can represent a transitional stage of differentiation. On the other side, Treg cells can differentiate independently of memory T cells and accumulate during life in the form of memory Treg cells. The supressor function of Tregs is also necessary as well as function of memory T cells to develop the immune response. It is possible, that a subset of Treg cells undergoes selection in thymus and constitutively express TCR-receptors having affinity with peripheral tissues. Further, these committed cells can be settled into tissues and become tissue-resident Treg cells which maintain regional T cell memory. Tregs can represent the “mirror image” of the structural organization of memory T cells, but with the return sign – the sign of suppression. The quantitative ratio of Tregs and memory T cells (CD4+CD45RO+CD25hiFoxP3+/CD4+CD45RO+CD25-FoxP3-), perhaps, is important criterion for functional assessment of immune system. The balance between these functionally opposite cell subsets has to provide stable functioning of immune system.

scholarly journals Successful Interference with Cellular Immune Responses to Immunogenic Proteins Encoded by Recombinant Viral Vectors

2001 ◽  
Vol 75 (1) ◽  
pp. 269-277 ◽  
Author(s):  
Adelaida Sarukhan ◽  
Sabine Camugli ◽  
Bernard Gjata ◽  
Harald von Boehmer ◽  
Olivier Danos ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
T Cell ◽  
Gene Transfer ◽  
Immune Responses ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cellular Immune Responses ◽  
Cellular Immune

ABSTRACT Vectors derived from the adeno-associated virus (AAV) have been successfully used for the long-term expression of therapeutic genes in animal models and patients. One of the major advantages of these vectors is the absence of deleterious immune responses following gene transfer. However, AAV vectors, when used in vaccination studies, can result in efficient humoral and cellular responses against the transgene product. It is therefore important to understand the factors which influence the establishment of these immune responses in order to design safe and efficient procedures for AAV-based gene therapies. We have compared T-cell activation against a strongly immunogenic protein, the influenza virus hemagglutinin (HA), which is synthesized in skeletal muscle following gene transfer with an adenovirus (Ad) or an AAV vector. In both cases, cellular immune responses resulted in the elimination of transduced muscle fibers within 4 weeks. However, the kinetics of CD4+ T-cell activation were markedly delayed when AAV vectors were used. Upon recombinant Ad (rAd) gene transfer, T cells were activated both by direct transduction of dendritic cells and by cross-presentation of the transgene product, while upon rAAV gene transfer T cells were only activated by the latter mechanism. These results suggested that activation of the immune system by the transgene product following rAAV-mediated gene transfer might be easier to control than that following rAd-mediated gene transfer. Therefore, we tested protocols aimed at interfering with either antigen presentation by blocking the CD40/CD40L pathway or with the T-cell response by inducing transgene-specific tolerance. Long-term expression of the AAV-HA was achieved in both cases, whereas immune responses against Ad-HA could not be prevented. These data clearly underline the importance of understanding the mechanisms by which vector-encoded proteins are recognized by the immune system in order to specifically interfere with them and to achieve safe and stable gene transfer in clinical trials.

scholarly journals Thymectomy in Juvenile Myasthenia Gravis Is Safe Regarding Long Term Immunological Effects

2021 ◽  
Vol 12 ◽  
Author(s):  
Trine H. Popperud ◽  
Kiran A. Gul ◽  
Cathrine Brunborg ◽  
Richard W. Olaussen ◽  
Tore G. Abrahamsen ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
T Cell ◽  
Myasthenia Gravis ◽  
Lower Number ◽  
Premature Aging ◽  
T Cell Subsets ◽  
Helper T Cells ◽  
Juvenile Myasthenia Gravis

Thymectomy is an established treatment in adult MG and also recommended for the treatment of post-pubertal onset juvenile MG. Whether the youngest children should be thymectomized is still debated. Signs of premature aging of the immune system have been shown in studies on early perioperative thymectomy in children with congenital heart defect. In this retrospective cohort study the objective was to investigate the long-term effects of treatment related thymectomy on T cell subsets and T cell receptor rearrangement excision circles (TRECs) in peripheral blood of juvenile myasthenia gravis (MG) patients, as well as clinical occurrence of autoimmune disorders, malignancies and infectious diseases. Forty-seven patients with onset of myasthenia gravis before the age of 19 years were included; 32 (68.1%) had been thymectomized and 15 (31.8%) had not. They were studied at varying times after thymectomy (7–26 years). We found a significant lower number of naïve helper T cells (CD4+CD45RA+) with an increased proportion of memory helper T cells (CD4+CD45RO+), and a significant lower number of naïve cytotoxic T cells (CD8+CD27+CD28+) in the thymectomized patients. In addition they showed a significant reduction in the number of TRECs and proportion of recent thymic emigrants (RTE) compared to non-thymectomized patients. In none of them an increased frequency of malignancies or infections was found. Our findings indicate a premature aging of the immune system after thymectomy in juvenile MG, but associated clinical consequences could not be verified.

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