scholarly journals Blood Absolute T Cell Counts may Predict 2-Month Treatment Response in Patients with Pulmonary Tuberculosis

2010 ◽  
Vol 28 (6) ◽  
pp. 343-352 ◽  
Author(s):  
Yung-Che Chen ◽  
Huang-Chih Chang ◽  
Chung-Jen Chen ◽  
Shih-Feng Liu ◽  
Chien-Hung Chin ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Treatment Response ◽  
Lymphocyte Subsets ◽  
Sputum Smear ◽  
Slow Response ◽  
Acid Fast Bacilli ◽  
Cell Counts ◽  
Bilateral Lung ◽  
Culture Positive

Background and objective:Little is known about the usefulness of lymphocyte subsets as early predictors of anti-tuberculosis (TB) treatment response in immuno-competent patients.Methods:Among a total of 64 patients with culture positive pulmonary TB, 29 remained sputum smear/culture positive or had delayed resolution on CXR (slow responders (SR)), and 35 had sputum culture conversion to negative and rapid resolution on CXR (fast responders (FR)) after two months of anti-tuberculosis treatment. Clinical parameters and lymphocyte subsets were investigated.Results:A larger proportion of patients in the SR group had cavities on CXR, bilateral lung involvement, positive acid-fast bacilli stains, and complaint of cough at diagnosis than those in the FR group. Absolute counts of CD3+T cells (p= 0.016) and CD8+T cells (p= 0.012) at diagnosis were both significantly higher in the SR group. This trend was present throughout the 6-month treatment course. Absolute T cell counts (odds ratio (OR) 1.002, 95% confidence interval (CI) 1.0–1.004), positive sputum acid fast bacilli stain (OR 6.69, 95% CI 1.37–32.77) and bilateral lung involvemment on CXR (OR 13.114, 95% CI 1.87–92.14) at diagnosis were independent predictors for a slow response. Combining these three predictors, a prediction score (PS) could be calculated to display an optimal discrimination for slow response (area under the curve (AUC) = 0.855,p< 0.001) whereas absolute T cell counts yielded the highest discriminative value on an individual level (AUC = 0.676,p= 0.015).Conclusions:A higher T cell count at diagnosis in patients with TB may predict a slow response to two months of treatment. The calculation of a PS further increased predictive accuracy and performance.

scholarly journals Distribution of Lymphocyte Subsets in Healthy Human Immunodeficiency Virus-Negative Adult Ethiopians from Two Geographic Locales

2001 ◽  
Vol 8 (6) ◽  
pp. 1171-1176 ◽  
Author(s):  
Afework Kassu ◽  
Aster Tsegaye ◽  
Beyene Petros ◽  
Dawit Wolday ◽  
Ermias Hailu ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
T Cell ◽  
Lymphocyte Subsets ◽  
Addis Ababa ◽  
Capital City ◽  
Healthy Human ◽  
Cell Counts ◽  
Hla Dr ◽  
Immunodeficiency Virus

ABSTRACT Immunological values for 562 factory workers from Wonji, Ethiopia, a sugar estate 114 km southeast of the capital city, Addis Ababa, Ethiopia, were compared to values for 218 subjects from Akaki, Ethiopia, a suburb of Addis Ababa, for whom partial data were previously published. The following markers were measured: lymphocytes, T cells, B cells, NK cells, CD4+ T cells, and CD8+ T cells. A more in depth comparison was also made between Akaki and Wonji subjects. For this purpose, various differentiation and activation marker (CD45RA, CD27, HLA-DR, and CD38) expressions on CD4+ and CD8+ T cells were studied in 60 male, human immunodeficiency virus-negative subjects (30 from each site). Data were also compared with Dutch blood donor control values. The results confirmed that Ethiopians have significantly decreased CD4+ T-cell counts and highly activated immune status, independent of the geographic locale studied. They also showed that male subjects from Akaki have significantly higher CD8+ T-cell counts, resulting in a proportional increase in each of the CD8+ T-cell compartments studied: naı̈ve (CD45RA+CD27+), memory (CD45RA−CD27+), cytotoxic effector (CD45RA+CD27−), memory/effector (CD45RA−CD27−), activated (HLA-DR+CD38+), and resting (HLA-DR−CD38−). No expansion of a specific functional subset was observed. Endemic infection or higher immune activation is thus not a likely cause of the higher CD8 counts in the Akaki subjects. The data confirm and extend earlier observations and suggest that, although most lymphocyte subsets are comparable between the two geographical locales, there are also differences. Thus, care should be taken in extrapolating immunological reference values from one population group to another.

scholarly journals Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients

2020 ◽  
Author(s):  
Jing Liu ◽  
Sumeng Li ◽  
Jia Liu ◽  
Boyun Liang ◽  
Xiaobei Wang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Prognostic Factor ◽  
Disease Severity ◽  
Peripheral Blood ◽  
Lymphocyte Subsets ◽  
Cytokine Profiles ◽  
Immune Parameters ◽  
Cell Counts ◽  
Novel Coronavirus

AbstractBackgroundThe dynamic changes of lymphocyte subsets and cytokines profiles of patients with novel coronavirus disease (COVID-19) and their correlation with the disease severity remain unclear.MethodsPeripheral blood samples were longitudinally collected from 40 confirmed COVID-19 patients and examined for lymphocyte subsets by flow cytometry and cytokine profiles by specific immunoassays.ResultsOf the 40 COVID-19 patients enrolled, 13 severe cases showed significant and sustained decreases in lymphocyte counts but increases in neutrophil counts than 27 mild cases. Further analysis demonstrated significant decreases in the counts of T cells, especially CD8 + T cells, as well as increases in IL-6, IL-10, IL-2 and IFN-γ levels in the peripheral blood in the severe cases compared to those in the mild cases. T cell counts and cytokine levels in severe COVID-19 patients who survived the disease gradually recovered at later time points to levels that were comparable to those of the mild cases. Moreover, the neutrophil-to-CD8+ T cell ratio (N8R) were identified as the most powerful prognostic factor affecting the prognosis for severe COVID-19.ConclusionsThe degree of lymphopenia and a proinflammatory cytokine storm is higher in severe COVID-19 patients than in mild cases, and is associated with the disease severity. N8R may serve as a useful prognostic factor for early identification of severe COVID-19 cases.SummaryLymphocyte subsets and cytokine profiles in the peripheral blood of COVID-19 patients were longitudinally characterized. The study revealed the kinetics features of immune parameters associated with the disease severity and identified N8R as a useful prognostic factor for predicting severe COVID-19 cases.

scholarly journals Lymphocyte subset analysis to evaluate the prognosis of HIV-negative patients with pneumocystis pneumonia

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Fan Jin ◽  
Jing Xie ◽  
Huan-ling Wang
Keyword(s):  
T Cell ◽  
Cell Count ◽  
Lymphocyte Subsets ◽  
Nk Cell ◽  
Cd8 T Cell ◽  
Pneumocystis Pneumonia ◽  
Lymphocyte Subset ◽  
Cd4 T Cell ◽  
Cell Counts ◽  
Hiv Negative

Abstract Objectives We analysed the peripheral blood lymphocyte subsets of human immunodeficiency virus (HIV)-negative patients infected with pneumocystis pneumonia (PCP) to determine the relationships between the levels of different types of lymphocytes and the prognosis of patients. Methods We retrospectively reviewed HIV-negative patients with PCP diagnosed in our department. All the eligible patients underwent lymphocyte subset analysis on admission. Results A total of 88 HIV-negative PCP patients were enrolled in the study. In univariate analyses, low CD4+ T cell count, low CD8+ T cell count, and low natural killer cell (NK cell) count were associated with higher in-hospital mortality. CD8+ T cell count ≤300/μL was found to be an independent risk factor for poor prognosis in multivariate logistical regression analysis (p = 0.015, OR = 11.526, 95% CI = 1.597–83.158). Although low CD4+ T cell and NK cell counts were not independent risk factors, the mortality rates of PCP patients decreased as the CD4+ T cell and NK cell counts increased. Conclusion The immune process of Pneumocystis jirovecii infection is complex but important. We propose that lymphocyte subsets could give clinicians a better understanding of patient immune status, helping with the early identification of potentially lethal infections and treatment decision making, such as adjusting the immunosuppressive regimen and choosing an appropriate patient monitoring level.

scholarly journals Long-Term Depletion of Naive T Cells in Patients Treated for Hodgkin's Disease

Blood ◽  
1997 ◽  
Vol 90 (9) ◽  
pp. 3662-3672 ◽  
Author(s):  
Nobukazu Watanabe ◽  
Stephen C. De Rosa ◽  
Anthony Cmelak ◽  
Richard Hoppe ◽  
Leonore A. Herzenberg ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Cell Subset ◽  
T Cell Subsets ◽  
Naive T Cells ◽  
Naïve T Cells ◽  
Cell Counts

Abstract We investigated the representation of T cells in patients who had been treated for Hodgkin's disease (HD). We found a marked depletion in both CD4 and CD8 naive T-cell counts that persists up to 30 years after completion of treatment. In contrast, CD4 and CD8 memory T-cell subsets recovered to normal or above normal levels by 5 years posttreatment. Thus, the previously-reported long-term deficit in total CD4 T-cell counts after treatment for HD is due to specific depletion of naive T cells. Similarly, total CD8 T-cell counts return to normal by 5 years only because CD8 memory T cells expand to higher than normal levels. These findings suggest that the treatment (mediastinal irradiation) results in a longterm dysregulation of T-cell subset homeostasis. The profound depletion of naive T cells may explain the altered T-cell function in treated patients, including the poor response to immunization after treatment for HD. Further, in some individuals, we identified expansions of unusual subsets expressing low levels of CD8. Eight-color fluorescence-activated cell sorting analyses showed that these cells largely express CD8αα homodimers and CD57, consistent with the phenotype of potentially extrathymically derived T cells. In addition, these cells, both CD4+ and CD4−, are probably cytotoxic lymphocytes, as they express high levels of intracellular perforin. In adults treated for HD, an increased activity of extrathymic T-cell differentiation may partially compensate for the loss of thymic-derived T cells.

scholarly journals Diet-Induced Obesity Promotes the Upregulation of Fas Expression on T-cells

Biology ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 217
Author(s):  
Tawanda Maurice Nyambuya ◽  
Phiwayinkosi Vusi Dludla ◽  
Bongani Brian Nkambule
Keyword(s):  
T Cells ◽  
Blood Glucose ◽  
T Cell ◽  
Total Cholesterol ◽  
White Cell Count ◽  
Fasting Blood Glucose ◽  
Monocyte Count ◽  
Diet Induced Obesity ◽  
Cell Counts ◽  
Body Weights

This study was conducted to assess the expression of Fas (CD95) and programmed cell death-1 (PD-1) on circulating T-cells in obesity using a diet-induced obesity mouse model. Furthermore, we aimed to determine if there are any associations between metabolic disorders and the expression of T-cell regulatory markers. A total of 12 male C57BL/6 mice were randomized into either a high-fat diet (HFD) or low-fat diet (LFD) group for 8 weeks (n = 6/group). Changes in body weights were monitored on a weekly basis. The lipid, glucose, and hematological profiles, as well as Fas and PD1 expression on the T-cell immunophenotype, were measured after 8 weeks of feeding. The HFD-fed group had a higher percentage weight gain (29.17%) in comparison with the LFD-fed group (21.74%) after the 8-week period. In addition, the HFD group had increased fasting glucose and glucose excursion following a 2-h postprandial period. The levels of total cholesterol were elevated in the HFD group when compared with the LFD group (p < 0.05). Notably, the absolute white cell count (p = 0.0096), neutrophil count (p = 0.0022, lymphocytes (p = 0.0155), and monocyte count (p = 0.0015) were elevated in the HFD group when compared with the LFD-fed group. However, the platelets (0.0680), red cell counts (0.3575), and their indices (p > 0.05) were comparable between the two groups. Interestingly, HFD feeding was associated with elevated expression of Fas on T-cells (p < 0.0001), which positively correlated with body weights (r = 0.93, p = 0.0333). No associations were found between Fas expression and dyslipidemia or fasting blood glucose levels (p > 0.05). The multivariant regression analysis showed that the association between the levels of Fas on T-cells and body weights (coefficient: −1.00, t-value: 19.27, p = 0.0330) was independent of fasting blood glucose, total cholesterol, and lymphocyte count. Lastly, the expression of PD-1 on T-cells was comparable between the two diet groups (p = 0.1822). In all, immune activation, dyslipidemia, and poor glucose control in the early stages of obesity may drive the pathogenesis of metabolic T-cell disorders. Importantly, T-cell dysfunction in obesity is partially mediated by an upregulation of Fas which is independent of dyslipidemia and hyperglycemia.

Overexpression of hTLX3 in Association with Mutant IL7Rα Is Sufficient to Generate T-ALL In Vivo and to Transform Thymocytes in Vitro

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 21-21
Author(s):  
Gisele Olinto Libanio Rodrigues ◽  
Julie Hixon ◽  
Hila Winer ◽  
Erica Matich ◽  
Caroline Andrews ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
T Cell ◽  
Cell Line ◽  
Lymphoblastic Leukemia ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Cell Counts

Mutations of the IL-7Rα chain occur in approximately 10% of pediatric T-cell acute lymphoblastic leukemia cases. While we have shown that mutant IL7Ra is sufficient to transform an immortalized thymocyte cell line, mutation of IL7Ra alone was insufficient to cause transformation of primary T cells, suggesting that additional genetic lesions may be present contributing to initiate leukemia. Studies addressing the combinations of mutant IL7Ra plus TLX3 overexpression indicates in vitro growth advantage, suggesting this gene as potential collaborative candidate. Furthermore, patients with mutated IL7R were more likely to have TLX3 or HOXA subgroup leukemia. We sought to determine whether combination of mutant hIL7Ra plus TLX3 overexpression is sufficient to generate T-cell leukemia in vivo. Double negative thymocytes were isolated from C57BL/6J mice and transduced with retroviral vectors containing mutant hIL7R plus hTLX3, or the genes alone. The combination mutant hIL7R wild type and hTLX3 was also tested. Transduced thymocytes were cultured on the OP9-DL4 bone marrow stromal cell line for 5-13 days and accessed for expression of transduced constructs and then injected into sublethally irradiated Rag-/- mice. Mice were euthanized at onset of clinical signs, and cells were immunophenotyped by flow cytometry. Thymocytes transduced with muthIL-7R-hTLX3 transformed to cytokine-independent growth and expanded over 30 days in the absence of all cytokines. Mice injected with muthIL7R-hTLX3 cells, but not the controls (wthIL7R-hTLX3or mutIL7R alone) developed leukemia approximately 3 weeks post injection, characterized by GFP expressing T-cells in blood, spleen, liver, lymph nodes and bone marrow. Furthermore, leukemic mice had increased white blood cell counts and presented with splenomegaly. Phenotypic analysis revealed a higher CD4-CD8- T cell population in the blood, bone marrow, liver and spleen compared in the mutant hIL7R + hTLX3 mice compared with mice injected with mutant IL7R alone indicating that the resulting leukemia from the combination mutant hIL7R plus hTLX3 shows early arrest in T-cell development. Taken together, these data show that oncogenic IL7R activation is sufficient for cooperation with hTLX3 in ex vivo thymocyte cell transformation, and that cells expressing the combination muthIL7R-hTLX3 is sufficient to trigger T-cell leukemia in vivo. Figure Disclosures No relevant conflicts of interest to declare.

scholarly journals Dynamics and Correlates of CD8 T-Cell Counts in Africans with Primary Human Immunodeficiency Virus Type 1 Infection

2016 ◽  
Vol 90 (22) ◽  
pp. 10423-10430 ◽  
Author(s):  
Heather A. Prentice ◽  
Hailin Lu ◽  
Matthew A. Price ◽  
Anatoli Kamali ◽  
Etienne Karita ◽  
...  
Keyword(s):  
T Cells ◽  
Viral Load ◽  
T Cell ◽  
Human Leukocyte ◽  
Neutralizing Antibody ◽  
Sensitivity Analyses ◽  
Supporting Evidence ◽  
Cell Counts ◽  
Cellular And Humoral Immunity ◽  
Hiv 1

ABSTRACT In individuals with HIV-1 infection, depletion of CD4 + T cells is often accompanied by a malfunction of CD8 + T cells that are persistently activated and/or exhausted. While the dynamics and correlates of CD4 counts have been well documented, the same does not apply to CD8 counts. Here, we examined the CD8 counts in a cohort of 497 Africans with primary HIV-1 infection evaluated in monthly to quarterly follow-up visits for up to 3 years in the absence of antiretroviral therapy. Statistical models revealed that (i) CD8 counts were relatively steady in the 3- to 36-month period of infection and similar between men and women; (ii) neither geography nor heterogeneity in the HIV-1 set-point viral load could account for the roughly 10-fold range of CD8 counts in the cohort ( P > 0.25 in all tests); and (iii) factors independently associated with relatively high CD8 counts included demographics (age ≤ 40 years, adjusted P = 0.010) and several human leukocyte antigen class I (HLA-I) alleles, including HLA-A*03:01 ( P = 0.013), B*15:10 ( P = 0.007), and B*58:02 ( P < 0.001). Multiple sensitivity analyses provided supporting evidence for these novel relationships. Overall, these findings suggest that factors associated with the CD8 count have little overlap with those previously reported for other HIV-1-related outcome measures, including viral load, CD4 count, and CD4/CD8 ratio. IMPORTANCE Longitudinal data from 497 HIV-1 seroconverters allowed us to systematically evaluate the dynamics and correlates of CD8 + T-cell counts during untreated primary HIV-1 infection in eastern and southern Africans. Our findings suggest that individuals with certain HLA-I alleles, including A*03 (exclusively A*03:01), persistently maintain relatively high CD8 counts following HIV-1 infection, a finding which may offer an intriguing explanation for the recently reported, negative association of A*03 with HIV-1-specific, broadly neutralizing antibody responses. In future studies, attention to HLA-I genotyping data may benefit in-depth understanding of both cellular and humoral immunity, as well as the intrinsic balances of these types of immunity, especially in settings where there is emerging evidence of antagonism between the two arms of adaptive immunity.

scholarly journals PIMATM point-of-care testing for CD4 counts in predicting antiretroviral initiation in HIV-infected individuals in KwaZulu-Natal, Durban, South Africa

2016 ◽  
Vol 17 (1) ◽  
Author(s):  
Mandisa Skhosana ◽  
Shabashini Reddy ◽  
Tarylee Reddy ◽  
Siphelele Ntoyanto ◽  
Elizabeth Spooner ◽  
...  
Keyword(s):  
South Africa ◽  
T Cells ◽  
T Cell ◽  
Antiretroviral Therapy ◽  
Cell Count ◽  
Point Of Care ◽  
Cd4 T Cell ◽  
Cell Counts ◽  
Kwazulu Natal ◽  
Cd4 T Cell Count

Introduction: Limited information is available on the usefulness of the PIMATM analyser in predicting antiretroviral treatment eligibility and outcome in a primary healthcare clinic setting in disadvantaged communities in KwaZulu-Natal, South Africa.Materials and methods: The study was conducted under the eThekwini Health Unit, Durban, KwaZulu-Natal. Comparison of the enumeration of CD4+ T-cells in 268 patients using the PIMATM analyser and the predicate National Health Laboratory Services (NHLS) was undertaken during January to July 2013. Bland-Altman analysis to calculate bias and limits of agreement, precision and levels of clinical misclassification at various CD4+ T-cell count thresholds was performed.Results: There was high precision of the PIMATM control bead cartridges with low and normal CD4+ T-cell counts using three different PIMATM analysers (%CV < 5). Under World Health Organization (WHO) guidelines (≤ 500 cells/mm3), the sensitivity of the PIMATM analyser was 94%, specificity 78% and positive predictive value (PPV) 95%. There were 24 (9%) misclassifications, of which 13 were false-negative in whom the mean bias was 149 CD4+ T-cells/mm3. Most (87%) patients returned for their CD4 test result but only 67% (110/164) of those eligible (≤ 350 cells/mm3) were initiated on antiretroviral therapy (ART) with a time to treatment of 49 days (interquartile range [IQR], 42–64 days).Conclusion: There was adequate agreement between PIMATM analyser and predicate NHLS CD4+ T-cell count enumeration (≤ 500 cells/mm3) in adult HIV-positive individuals. The high PPV, sensitivity and acceptable specificity of the PIMATM analyser technology lend it as a reliable tool in predicting eligibility and rapid linkage to care in ART programmes.Keywords: HIV; Point of Care; PIMATM CD4+ T cell counts; antiretroviral therapy; prediction/eligibility; South Africa

scholarly journals Lymphocyte subset alterations with disease severity, imaging manifestation, and delayed hospitalization in COVID-19 patients

2020 ◽  
Author(s):  
Daxian Wu ◽  
Xiaoping Wu ◽  
Jiansheng Huang ◽  
Qunfang Rao ◽  
Qi Zhang ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Cell Count ◽  
Disease Severity ◽  
Lymphocyte Subsets ◽  
Nk Cell ◽  
Lymphocyte Subset ◽  
Multivariate Logistic Regression ◽  
Cell Counts ◽  
Glutamyl Transpeptidase

Abstract Background: COVID-19 continuously threated public health heavily. Present study aimed to investigate the lymphocyte subset alterations with disease severity, imaging manifestation, and delayed hospitalization in COVID-19 patients.Methods: Lymphocyte subsets was classified using flow cytometry with peripheral blood collected from 106 patients.Results: Multivariate logistic regression showed that chest tightness, lymphocyte count, and γ-glutamyl transpeptidase were the independent predictors for severe COVID-19. The T cell, CD4+ T cell and B cell counts in severe patients were significantly lower than that in mild patients (p = 0.004, 0.003 and 0.046, respectively). Only the T cell count was gradually decreased with the increase of infiltrated quadrants of lesions in computed tomography (CT) (p = 0.043). The T cell, CD4+ T cell, and CD8+ T cell counts were gradually decreased with the increase of infiltrated area of the maximum lesion in CT (p = 0.002, 0.003, 0.028; respectively). The T cell count, as well as CD4+ T cell, CD8+ T cell, and NK cell counts were gradually decreased with the increased delayed hospitalization (p = 0.003, 0.002, 0.013, and 0.012; respectively). The proportion of T cell was gradually decreased but B cell was gradually increased with the increased delayed hospitalization (p = 0.031 and 0.003, respectively).Conclusion: T cell and CD4+ T cell counts negatively correlated with disease severity, CT manifestation and delayed hospitalization. CD4+ T cell was mainstay of immunity response in COVID-19 patients.

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.

Sign in / Sign up

Export Citation Format

Share Document