scholarly journals Phenotype of recovering lymphoid cell populations after marrow transplantation.

1985 ◽  
Vol 161 (6) ◽  
pp. 1483-1502 ◽  
Author(s):  
K A Ault ◽  
J H Antin ◽  
D Ginsburg ◽  
S H Orkin ◽  
J M Rappeport ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Nk Cells ◽  
Cell Types ◽  
Lymphoid Cells ◽  
The Other ◽  
Hla Dr ◽  
T Cell Antigens ◽  
Leu 7

Four patients who received bone marrow transplants were studied sequentially during the posttransplant period to define the pattern of recovering lymphoid cell types. Three patients received T cell-depleted, HLA-matched marrow, and one received untreated marrow from an identical twin. Blood lymphoid cells were labeled with 25 different pairs of monoclonal antibodies. In each sample, one antibody was conjugated to fluorescein and one to phycoerythrin, thus allowing simultaneous assessment of the expression of the two markers using the fluorescence activated cell sorter. A total of 14 antibodies were used, routinely including HLE, Leu-M3, Leu-4, Leu-1, Leu-5, Leu-9, Leu-6, Leu-2, Leu-3, HLA-DR, Leu-7, Leu-11, Leu-15, and Leu-12. Other antibodies were used to further define some populations. This study has allowed us to define six distinct cell types that have appeared in all four patients by day 90 posttransplantation, and which account for 90-100% of all circulating lymphoid cells. These cell types are (a) T helper cells expressing Leu-1, Leu-4, Leu-9, Leu-5, Leu-3, and variable amounts of HLA-DR; (b) T suppressor cells expressing Leu-1, Leu-4, Leu-9, Leu-5, Leu-2, and variable amounts of HLA-DR; (c) B cells expressing Leu-12, B1, HLA-DR, IgD, and IgM, but none of the T cell antigens; (d) an unusual B cell phenotype (Leu-1 B) expressing all of the B cell markers, and also having low amounts of Leu-1, but none of the other T cell antigens; (e) natural killer (NK) cells expressing Leu-11, Leu-15, Leu-5 but none of the other T cell or B cell markers; (f) NK cells expressing Leu-11, Leu-15, Leu-5, and low levels of Leu-2. Both NK types also express Leu-7 on some, but not all cells. The relative frequencies of these cell types varied among the patients and with time, but the striking findings were the presence of relatively few mature T cells, large numbers of NK cells, and the preponderance of the unusual Leu-1 B cell over conventional B cells in all three patients who developed B cells. Sorting experiments confirmed the NK activity of the major NK cell phenotypes, and DNA analysis confirmed that all of the cells studied were of donor origin. In addition, analysis of Ig genes in one patient showed that the Leu-1 B cells were not clonally rearranged.(ABSTRACT TRUNCATED AT 400 WORDS)

A New Platform For Trivalent Bispecific Antibodies Used For T-Cell Redirected Killing Of B-Cell Malignancies

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3078-3078
Author(s):  
Diane L Rossi ◽  
Edmund A Rossi ◽  
David M Goldenberg ◽  
Chien-Hsing Chang
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Cell Surface ◽  
B Cell ◽  
Tumor Cells ◽  
Stock Option ◽  
B Cell Malignancies ◽  
Hla Dr ◽  
Close Proximity

Abstract Background Various formats of bispecific antibodies (bsAbs) to redirect effector T cells for the targeted killing of tumor cells have shown considerable promise both pre-clinically and clinically. The scFv-based constructs, including BiTE and DART, which bind monovalently to CD3 on T cells and to the target antigen on tumor cells, exhibit fast blood clearance and neurological toxicity due to their small size (∼55 kDa). Herein, we describe the generation of novel T-cell redirecting trivalent bsAbs comprising an anti-CD3 scFv covalently conjugated to a stabilized F(ab)2. The design was initially characterized with a prototype construct designated (19)-3s, which specifically targets CD19 on B cells. A panel of trivalent bsAbs was evaluated for their potential use in targeted T-cell immunotherapy of various B-cell malignancies. Potential advantages of this design include bivalent binding to tumor cells, a larger size (∼130 kDa) to preclude rapid renal clearance and penetration of the blood-brain barrier, and potent T-cell mediated cytotoxicity. Methods The DOCK-AND-LOCKTM (DNLTM) method was used to generate a panel of B-cell targeting bsAbs, (19)-3s, (20)-3s, (22)-3s, and (C2)-3s, which target CD19, CD20, CD22, and HLA-DR, respectively. This was achieved by combining a stabilized anti-X F(ab)2 with an anti-CD3-scFv, resulting in a homogeneous covalent structure of the designed composition, as shown by LC-MS, SE-HPLC, ELISA, SDS-PAGE, and immunoblot analyses. Each construct can mediate the formation of immunological synapses between T cells and malignant B cells, resulting in T-cell activation. At an E:T ratio of 10:1, using isolated T cells as effector cells, the bsAbs induced potent T-cell-mediated cytotoxicity in various B-cell malignancies, including Burkitt lymphomas (Daudi, Ramos, Namalwa), mantle cell lymphoma (Jeko-1), and acute lymphoblastic leukemia (Nalm-6). A non-tumor binding control, (14)-3s, induced only moderate T-cell killing at >10 nM. The nature of the antigen/epitope, particularly its size and proximity to the cell surface, appears to be more important than antigen density for T-cell retargeting potency (Table 1). It is likely that (20)-3s is consistently more potent than (19)-3s and (C2)-3s, even when the expression of CD19 or HLA-DR is considerably higher than CD20, as seen with Namalwa and Jeko-1, respectively. This is likely because the CD20 epitope comprises a small extracellular loop having close proximity to the cell surface. When compared directly using Daudi, (22)-3s was the least potent. Compared to CD19 and CD20, CD22 is expressed at the lowest density, is a rapidly internalizing antigen, and its epitope is further away from the cell surface; each of these factors may contribute to its reduced potency. Finally, sensitivity to T-cell retargeted killing is cell-line-dependent, as observed using (19)-3s, where Raji (IC50 >3 nM) is largely unresponsive yet Ramos (IC50 = 2 pM) is highly sensitive, even though the former expresses higher CD19 antigen density. Conclusions (19)-3s, (20)-3s, (22)-3s, and (C2)-3s can bind T cells and target B cells simultaneously and induce T-cell-mediated killing in vitro. The modular nature of the DNL method allowed the rapid production of several related conjugates for redirected T-cell killing of various B-cell malignancies, without the need for additional recombinant engineering and protein production. The close proximity of the CD20 extracellular epitope to the cell surface results in the highest potency for (20)-3s, which is an attractive candidate bsAb for use in this platform. We are currently evaluating the in vivo activity of these constructs to determine if this novel bsAb format offers additional advantages. Disclosures: Rossi: Immunomedics, Inc.: Employment. Rossi:Immunomedics, Inc.: Employment. Goldenberg:Immunomedics: Employment, stock options, stock options Patents & Royalties. Chang:Immunomedics, Inc: Employment, Stock option Other; IBC Pharmaceuticals, Inc.: Employment, Stock option, Stock option Other.

Rapid Immunoprofiling of New Lymphocytosis Cases Using a Routine Hematology Analyzer: A Multicenter Study.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1532-1532
Author(s):  
Henk Adriaansen ◽  
Gita A van den Berg ◽  
Martin H. Herruer ◽  
Joost Schuitemaker ◽  
Jan W. Smit ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Nk Cells ◽  
Screening Strategy ◽  
Cell Counts ◽  
Hla Dr ◽  
Hematology Analyzer ◽  
Potentially Malignant ◽  
Mixed Pattern

Abstract Introduction: Lymphocytosis is a frequent finding in the routine hematology laboratory. Most often, lymphocytosis is caused by a reactive increase of T-, B- and/or NK-lymphocytes, but it may represent the first sign of a malignant monoclonal B-cell disorder as well. Currently, it is common practice in mild and moderate lymphocytosis to follow up the patient for three months in order to see whether this condition is chronic. If the lymphocytosis proves to be persistent, immunophenotyping is necessary to establish whether a reactive or a malignant disorder is causing it. It is not unusual that patients become concerned during this period as to the nature of their disease. Although the finding of lymphocytosis and/or instrument flagging may result in a manual differentiation and probably in detecting morphologic abnormalities in the lymphocytes, direct immunophenotyping is preferable to a manual differentiation, since morphology is not sufficiently sensitive and specific. However, immunophenotyping is time-consuming, expensive and until now only available in specialized laboratories. A rapid immunological screening (immunoprofile) could help reducing the number of extensive immunophenotypes. Moreover, patients with newly found lymphocytosis and their physicians may appreciate to have a more rapid indication on the nature of the lymphocytosis. Therefore, we studied the feasibility of a rapid immunoprofile, using a routine hematology analyzer, immediately after a new lymphocytosis case was detected. It was not our goal to provide a final immunophenotype, but rather an indication whether the lymphocytosis is reactive or potentially malignant. In the latter case, a full immunophenotype would still be necessary. Methods: Five hospital laboratories investigated all samples with previously unknown lymphocyte count > 5.0 109/L or a variant lymphocyte flag from patients over 12 years of age. The immunologic analysis was performed on the same blood sample within 24 hours from collection. Six pairs of monoclonal antibodies were used: CD3/4, CD3/8, CD3/19, CD3/16+56, CD3/5 and CD3/HLA-Dr (each pair FITC/PE labeled, respectively; IQ Products, Groningen, the Netherlands). The analysis was carried out using the fully automated CELL-DYN Sapphire hematology analyzer (Abbott Diagnostics, Santa Clara, CA, USA) and FCS files were collected. Data analysis of the FCS files was done centrally using commercial flow cytometry software (WinList; Verity Software House, Topsham, ME, USA). Results: In total, the five laboratories analyzed 111 patient samples meeting the inclusion criteria. Of these patients, the majority showed a mixed pattern of increased T-cells together with B- and/or NK-cells (n=59; 53%). In 14 patients (13%), only T-cell counts were increased; no patient had increased NK-cells only and 34 patients (31%) showed increased B-cells. The remaining 4 patients (4%) could not be classified unambiguously. Of the 34 patients with increased B-cells, 25 had approximately equal numbers of CD5+ and 19+ lymphocytes, which is highly suggestive of a CLL phenotype. There were no cases in which the lymphocytosis would have been classified differently, if the HLA-Dr antibody had been omitted. Thus, the immunoprofile can be further limited without losing information as to the nature of the lymphocytosis. Discussion: The majority of patients in our study (73; 66%) had reactive lymphocytosis. In addition, 25 patients (23%) had CD5+, CD19+ B-cell lymphocytosis, suggestive of CLL or monoclonal B-cell lymphocytosis. The latter group needs additional immunological investigation and further clinical follow-up. By using this immunoprofile screening strategy, the number of full immunophenotypes could be reduced by approximately two thirds, which means a significant reduction in workload and cost to the laboratory. Conclusion: We have shown that it is well feasible to rapidly discriminate reactive from potentially malignant causes in patients with newly established lymphocytosis. The incidence of lymphocytosis with CLL-like phenotype amounted to 23% in our study, which is higher than reported so far in the literature.

Perturbation of B-cell development in mice overexpressing the Bcl-2 homolog A1

Blood ◽  
2002 ◽  
Vol 99 (9) ◽  
pp. 3350-3359 ◽  
Author(s):  
Peter I. Chuang ◽  
Samantha Morefield ◽  
Chien-Ying Liu ◽  
Stephen Chen ◽  
John M. Harlan ◽  
...  
Keyword(s):  
Immune System ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
System Development ◽  
Cell Development ◽  
B Cell Development ◽  
Lymphoid Cells ◽  
Immune System Development ◽  
And Function

Abstract Decisions about cell survival or death are central components of adaptive immunity and occur at several levels in immune system development and function. The Bcl-2 family of homologous proteins plays an important role in these decisions in lymphoid cells. Bcl-2, Bcl-xL, and A1 are differentially expressed during B- and T-cell development, and they have shared and distinct roles in regulating cell death. We sought to gain insight into the role of A1 in immune system development and function. A murine A1-a transgene was expressed under the control of the Eμ enhancer, and mice with A1 overexpression in B- and T-cell lineages were derived. Thymocytes and early B cells in Eμ-A1 mice showed extended survival. B-lineage development was altered, with expansion of the pro–B cell subset at the expense of pre–B cells, suggesting an impairment of the pro– to pre–B-cell transition. This early B-cell phenotype resembled Eμ–Bcl-xL mice but did not preferentially rescue cells with completed V(D)J rearrangements of the immunoglobulin heavy chain. In contrast to Eμ–Bcl-2 transgenes, A1 expression in pro–B cells did not rescue pre–B-cell development in SCID mice. These studies indicate that A1 protects lymphocytes from apoptosis in vitro but that it has lineage- and stage-specific effects on lymphoid development. Comparison with the effects of Bcl-2 and Bcl-xL expressed under similar control elements supports the model that antiapoptotic Bcl-2 homologs interact differentially with intracellular pathways affecting development and apoptosis in lymphoid cells.

scholarly journals Antiproliferative effect of antilymphocyte globulins on B cells and B- cell lines

Blood ◽  
1992 ◽  
Vol 79 (8) ◽  
pp. 2164-2170
Author(s):  
N Bonnefoy-Berard ◽  
M Flacher ◽  
JP Revillard
Keyword(s):  
Cell Proliferation ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cell Lines ◽  
Immunosuppressive Agents ◽  
Lymphoproliferative Disorders ◽  
Hla Dr ◽  
T Cell Lines ◽  
Vitro Effect

Antithymocyte and antilymphocyte globulins (ALG) are currently used as immunosuppressive agents in organ transplantation and for the treatment of acute graft-versus-host disease and aplastic anemia. Since any type of immunosuppressive treatment is known to carry the risk of developing B-cell lymphoproliferative disorders, we investigated the in vitro effect of ALG on human B-cell activation and proliferation. The data demonstrate that whatever the source of lymphocytes used for ALG preparation (thymocytes, thoracic duct lymphocytes, B- or T-cell lines), (1) ALG react with both B- and T-cell lines, and (2) ALG contain antibodies specific for B cells (eg, CD21) or common to T and B cells (eg anti-beta 2-microglobulin, anti-HLA-DR, CD18, CD11a) in addition to T-cell-specific antibodies. Unlike all other T-cell mitogens tested (Concanavalin A [Con A], Pokeweek mitogen [PWM], CD3 and CD2 antibodies), ALG do not trigger B-cell differentiation into immunoglobulin-secreting cells at concentrations which induce maximum T- cell proliferation. This effect could be attributed to a direct interaction of ALG with B lymphocytes as shown by the capacity of ALG to block the response of purified B cells to a variety of activators. Furthermore, all the ALG tested were shown to inhibit the proliferation of six of the seven Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines and six of the seven Burkitt's lymphoma cell lines studied. This selective B-cell antiproliferative property of ALG was not reproduced with CD11a, CD18, CD21, CD24, or anti-HLA-DR monoclonal antibodies (MoAbs). These results suggest that, although suppressing T- cell responses, ALG treatment may directly control B cell proliferation to some extent, in keeping with the relatively low risk of posttransplant lymphoproliferative disorders reported with ALG.

A Profile of 648 Signaling Network Events Identifies Cell Subsets with Diverse, Abnormal Responses to Lymphocyte Stimuli within Follicular Lymphoma Tumors.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 356-356 ◽  
Author(s):  
Jonathan M. Irish ◽  
Faye Y. Hsu ◽  
Jeff P. Sharman ◽  
Roch Houot ◽  
Joshua D. Brody ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Follicular Lymphoma ◽  
B Cell ◽  
Cell Survival ◽  
Signaling Network ◽  
Lymphoid Cells ◽  
Network Activity ◽  
T Cell Subsets

Abstract Signal transduction plays a key role in cell survival, and changes to signaling are frequently implicated in tumor initiation and progression. We sought to identify abnormal variation in signaling network activity within primary tumor samples obtained prior to treatment from patients with follicular lymphoma (FL). We previously showed that altered B cell receptor (BCR) signaling distinguishes tumor B cells from the non-malignant host B cells in FL tumors. Here we extend this approach and use flow cytometry to measure 648 signaling events in live lymphoid cells from more than 25 lymphoma specimens and healthy controls. We combined 9 previously identified BCR stimulation conditions with inputs from CD40, interleukin 4, interferons (IFNs), and more than 10 other environmental cues that govern the development and activity of lymphocytes. Fluorescent cell barcoding allowed simultaneous staining and analysis of phospho-protein activation under all 27 stimulation conditions within a single tube. The activation of key phospho-protein nodes throughout lymphocyte signaling networks, including Syk, Erk1/2, Btk, Src family kinases, cCbl, p38, NFkB, Akt, Stat1, Stat3, Stat6, and Stat5, was measured under each of the 27 stimulation conditions. Measurements of phospho-protein responses to stimulation were combined with detection of the Bcl-2 oncogene, B and T cell lineage markers in each cell. This panel allowed us to characterize signaling in the heterogeneous cell subsets found within each patient’s tumor sample. Tumor B cells, host tumor infiltrating T cells, non-malignant B cells were all distinguished by contrasting signaling profiles. In some cases, subsets of tumor B cells with differences in signaling network topology were observed within the tumor B cell population. This result suggests that signaling can distinguish between tumor sub-clones and could be used to measure tumor heterogeneity. As previously reported, little variation in signaling was observed among healthy peripheral blood B and T cell samples from different individuals. Abnormally low host T cell signaling was commonly observed within the tumor infiltrating T cells infiltrating FL tumors. Further analysis of tumor T cell subsets indicated that a high proportion of infiltrating T cells expressed CD4 and FoxP3. Taken together, these results support the hypothesis that FL tumor B cells promote suppressed signaling in the T cells of the patient and may modulate the immune response against the tumor. In FL tumor B cells, BCR and IFN signaling frequently triggered Stat5 phosphorylation, but not Stat1 phosphorylation. These results are consistent with the hypothesis that Stat5 initiates genetic programs that support cancer cell survival and proliferation, whereas Stat1 promotes immunogenicity and cooperates with the p53 tumor suppressor protein. In contrast with healthy B cells, loss of the response to CD40L, altered PKC signaling, and variable responses to BCR crosslinking were all seen in FL tumor B cells. The patterns of abnormal signaling we observed in tumor B cells and tumor infiltrating T cells suggest that measuring the activity of key signaling network nodes can identify targets for therapeutic attention in FL.

scholarly journals Antiproliferative effect of antilymphocyte globulins on B cells and B- cell lines

Blood ◽  
1992 ◽  
Vol 79 (8) ◽  
pp. 2164-2170 ◽  
Author(s):  
N Bonnefoy-Berard ◽  
M Flacher ◽  
JP Revillard
Keyword(s):  
Cell Proliferation ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cell Lines ◽  
Immunosuppressive Agents ◽  
Lymphoproliferative Disorders ◽  
Hla Dr ◽  
T Cell Lines ◽  
Vitro Effect

Abstract Antithymocyte and antilymphocyte globulins (ALG) are currently used as immunosuppressive agents in organ transplantation and for the treatment of acute graft-versus-host disease and aplastic anemia. Since any type of immunosuppressive treatment is known to carry the risk of developing B-cell lymphoproliferative disorders, we investigated the in vitro effect of ALG on human B-cell activation and proliferation. The data demonstrate that whatever the source of lymphocytes used for ALG preparation (thymocytes, thoracic duct lymphocytes, B- or T-cell lines), (1) ALG react with both B- and T-cell lines, and (2) ALG contain antibodies specific for B cells (eg, CD21) or common to T and B cells (eg anti-beta 2-microglobulin, anti-HLA-DR, CD18, CD11a) in addition to T-cell-specific antibodies. Unlike all other T-cell mitogens tested (Concanavalin A [Con A], Pokeweek mitogen [PWM], CD3 and CD2 antibodies), ALG do not trigger B-cell differentiation into immunoglobulin-secreting cells at concentrations which induce maximum T- cell proliferation. This effect could be attributed to a direct interaction of ALG with B lymphocytes as shown by the capacity of ALG to block the response of purified B cells to a variety of activators. Furthermore, all the ALG tested were shown to inhibit the proliferation of six of the seven Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines and six of the seven Burkitt's lymphoma cell lines studied. This selective B-cell antiproliferative property of ALG was not reproduced with CD11a, CD18, CD21, CD24, or anti-HLA-DR monoclonal antibodies (MoAbs). These results suggest that, although suppressing T- cell responses, ALG treatment may directly control B cell proliferation to some extent, in keeping with the relatively low risk of posttransplant lymphoproliferative disorders reported with ALG.

scholarly journals Establishing Phenotypic Features Associated with Morbidity in Human T-Cell Lymphotropic Virus Type 1 Infection

2004 ◽  
Vol 11 (6) ◽  
pp. 1105-1110 ◽  
Author(s):  
G. E. A. Brito-Melo ◽  
J. G. Souza ◽  
E. F. Barbosa-Stancioli ◽  
A. B. F. Carneiro-Proietti ◽  
B. Catalan-Soares ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
T Lymphocytes ◽  
B Cell ◽  
Virus Type ◽  
Peripheral Blood ◽  
Cell Ratio ◽  
Human T Cell ◽  
Hla Dr

ABSTRACT The human T-cell lymphotropic virus type 1 (HTLV-1) is the causative agent of HTLV-1-associated myelopathy/tropical spastic paraparesis (HT). Although it is widely believed that virus infection and host immune response are involved in the pathogenic mechanisms, the role of the immune system in the development and/or maintenance of HT remains unknown. We performed an analysis of the peripheral blood leukocyte phenotype for two different subcohorts of HTLV-1-infected individuals to verify the existence of similar immunological alterations, possible laboratory markers for HT. The leukocyte population balance, the activation status of the T lymphocytes, and the cellular migratory potential of T lymphocytes, monocytes, and neutrophils were evaluated in the peripheral blood of HTLV-1-infected individuals classified as asymptomatic individuals, oligosymptomatic individuals, and individuals with HT. Data analysis demonstrated that a decreased percentage of B cells, resulting in an increased T cell/B cell ratio and an increase in the CD8+ HLA-DR+ T lymphocytes, exclusively in the HT group could be identified in both subcohorts, suggesting its possible use as a potential immunological marker for HT for use in the laboratory. Moreover, analysis of likelihood ratios showed that if an HTLV-1-infected individual demonstrated B-cell percentages lower than 7.0%, a T cell/B cell ratio higher than 11, or a percentage of CD8+ HLA-DR+ T lymphocytes higher than 70.0%, this individual would have, respectively, a 12-, 13-, or 22-times-greater chance of belonging to the HT group. Based on these data, we propose that the T cell/B cell ratios and percentages of circulating B cells and activated CD8+ T lymphocytes in HTLV-1-infected patients are important immunological indicators which could help clinicians monitor HTLV-1 infection and differentiate the HT group from the asymptomatic and oligosymptomatic groups.

scholarly journals Effects of Morbid Obesity and Metabolic Syndrome on the Composition of Circulating Immune Subsets

2021 ◽  
Vol 12 ◽  
Author(s):  
Leontine H. Wijngaarden ◽  
Erwin van der Harst ◽  
René A. Klaassen ◽  
Martin Dunkelgrun ◽  
T Martijn Kuijper ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Morbid Obesity ◽  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Nk Cells ◽  
Cd8 T Cells ◽  
Monocyte Subsets ◽  
The Absolute

Morbid obesity is characterized by chronic, low-grade inflammation, which is associated with ‘inflamm-aging’. The presence of metabolic syndrome (MetS) might accelerate this phenomenon of metaflammation. In this study, we assessed the effects of morbid obesity and MetS on the composition of a broad spectrum of immune cells present within the circulation. A total of 117 morbidly obese patients (MOP) without MetS (MetS-), 127 MOP with MetS (MetS+) and 55 lean controls (LC) were included in this study. Absolute numbers of T cell, B cell, NK cell and monocyte subsets were assessed within peripheral blood using flow cytometry. Both absolute cell numbers and proportion of cells were evaluated correcting for covariates age, body mass index and cytomegalovirus serostatus. Although the absolute number of circulating CD4+ T cells was increased in the MetS+ group, the CD4+ T cell composition was not influenced by MetS. The CD8+ T cell and B cell compartment contained more differentiated cells in the MOP, but was not affected by MetS. Even though the absolute numbers of NK cells and monocytes were increased in the MOP as compared to LC, there was no difference in proportions of NK and monocyte subsets between the three study groups. In conclusion, although absolute numbers of CD4+ and CD8+ T cells, B cells, NK cells and monocytes are increased in MOP, obesity-induced effects of the composition of the immune system are confined to a more differentiated phenotype of CD8+ T cells and B cells. These results were not affected by MetS.

scholarly journals Peripheral blood lymphocytes and monocytes heterogeneity in SLE patients treated by Belimumab

2021 ◽  
Author(s):  
Jinghan Yang ◽  
Shushan Yan ◽  
Haibo Li ◽  
Chunjuan Yang ◽  
Lili Zhang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Nk Cells ◽  
Lupus Erythematosus ◽  
Peripheral Blood ◽  
Peripheral Blood Lymphocytes ◽  
Systemic Lupus ◽  
Blood Lymphocytes ◽  
Hla Dr

Abstract Objective: To estimate the effect of Belimumab on the heterogeneity of peripheral blood lymphocytes and monocytes subsets in systemic lupus erythematosus (SLE).Methods: There were three groups of populations, namely health controls (HC, n = 92), SLE patients treated (n = 26) and un-treated with BAFF (n = 155) in the present study. Cell subsets of CD3+T cells, CD3+CD4+T cells, CD3+CD8+T cells, CD19+B cells, CD16+CD56+NK cells, CD14+HLA-DR+monocytes, CD14+CD206+monocytes and CD14+CD163+monocytes were estimated by flow cytometry. Results: Compared with HC group, SLE patients had a higher level of CD3+T cells and CD3+CD8+T cells, but a lower level of CD3+CD4+T cells, CD16+CD56+NK cells, CD14+CD206+monocytes, and CD14+CD163+monocytes. Besides, the ratio of CD3+CD4+/CD3+CD8+T cells was much lower in SLE patients. Belimumab could effectively decrease CD19+B cells but increase CD3+T cell and CD3+CD8+T cells in the peripheral blood of SLE patients. Moreover, SLE patients had decreased CD14+CD206+ monocytes and CD14+CD163+ monocytes in peripheral blood, while Belimumab therapy did not affect the heterogeneity of monocytes in SLE.Conclusions: Our results revealed the heterogeneity of lymphocytes and monocytes in SLE patients. The clinical efficacy of Belimumab in SLE treatment is remarkable due to its significant effect on down-regulating B cell but up-regulating CD3+T cell and CD3+CD8+T cells in SLE.

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