Increased Number of B-Cells In the Red Pulp of the Spleen In ITP

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1447-1447
Author(s):  
Bob Olsson ◽  
Hans Wadenvik ◽  
Margareta Jernås ◽  
Börje Ridell
Keyword(s):  
T Cells ◽  
Platelet Count ◽  
B Cells ◽  
Lymphocyte Subsets ◽  
Conflicts Of Interest ◽  
Cytotoxic T Cells ◽  
Splenic Tissue ◽  
White Pulp ◽  
Chronic Itp ◽  
Red Pulp

Abstract Abstract 1447 Background. Platelets are targeted by autoantibodies and destroyed in the reticuloendothelial system, e.g. the spleen, in patients with chronic immune thrombocytopenia (ITP). However, other pathophysiologic mechanisms such as platelet destruction by cytotoxic T-cells and defective bone marrow production of platelets also contribute to the thrombocytopenia in ITP. Splenectomy normalizes the platelet count in around 70% of chronic ITP patients, however, precious little is known about the spleen micromorphology in this disease. We examined splenic pathology in patients with ITP, focusing on the intrasplenic distribution of lymphocyte subsets. Patients and Methods. The paraffin-embedded block containing representative material of the splenic tissue from 29 splenectomized chronic ITP patients (15 females and 14 males, mean age 45±21 (SD) years) and 11 controls, splenectomized because of traumatic splenic rupture (2 females and 9 males, mean age 48±19 (SD) years), was used to produce serial sections with a thickness of 5 μm. These sections were stained with conventional haematoxylin-eosin, and immunostained to identify CD3, CD4, CD8, CD20 and CD68 using the Dako Envision System in a Techmate Horizon Autostainer (Glostrup, Denmark). Using micromorphometry the lymphocyte subsets were enumerated in the red and white pulp of these spleens. Results. All ITP patients were preoperatively optimized, using corticosteroids and/or IVIg, and the immediate pre-splenectomy platelet count ranged 5–357 × 109/l. Significantly more T-cells than B-cells were seen in the red pulp, both in ITP and control spleens (p<0.01). Conversely, more B-cells than T-cells were observed in the white pulp. There was no difference in the number of T-cells in the red and white pulp, between ITP patients and controls. However, the number of B-cells was increased in the red pulp of patients with ITP compared with the controls. Furthermore, numerous B-cells and CD8+ (cytotoxic) T-cells were located in the splenic cords, lining the sinusoids in the red pulp, a microenvironment where they readily can interact with the other blood cells, e.g. platelets. Conclusion. Chronic ITP is associated with an increased number of CD20+ B-cells in the red pulp of the spleen. The red pulp of the spleen also provides a microenvironment where close interaction between platelets, CD3+, CD4+, and CD8+ T-cells and B-cells can take place. Trafficking of regulatory and effector cells into this microenvironment might be a potential therapeutic target. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Reactive lymphocytes in lacrimal gland and vasculitic renal lesions of autoimmune MRL/lpr mice express L3T4.

1987 ◽  
Vol 166 (4) ◽  
pp. 1198-1203 ◽  
Author(s):  
D A Jabs ◽  
R A Prendergast
Keyword(s):  
T Cells ◽  
B Cells ◽  
Lacrimal Gland ◽  
Lymphocyte Subsets ◽  
Cytotoxic T Cells ◽  
Immunologic Response ◽  
Inflammatory Lesions ◽  
Renal Lesions ◽  
Renal Vasculitis ◽  
Reactive Lymphocytes

The lacrimal gland inflammatory lesions and renal vasculitic lesions of autoimmune MRL/lpr mice were analyzed for the lymphocyte subsets present. The majority of cells were Thy-1.2+ T cells (mean, 85%) of the L3T4+ helper T phenotype (mean, 64 and 58%, respectively). Lesser numbers of Lyt-2+ suppressor/cytotoxic T cells, B cells, and macrophages were present. The finding that the majority of lymphocytes in both the lacrimal gland inflammatory lesions and renal vasculitis of MRL/lpr mice expressed L3T4 suggests that these cells may be capable of responding to antigen presentation and that an active immunologic response occurs at these sites.

CD137/4-1BB Is Inducibly Expressed On CLL B Cells through CD40 Signaling.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1266-1266
Author(s):  
Tetsuya Fukuda ◽  
Yukana Nakaima ◽  
Aya Kasubata ◽  
Ken Watanabe ◽  
Takatoshi Koyama ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Nuclear Translocation ◽  
Conflicts Of Interest ◽  
Cytotoxic T Cells ◽  
Cd40 Ligation ◽  
Activated T Cells ◽  
Blocking Antibody ◽  
Healthy Donors

Abstract Abstract 1266 Poster Board I-288 CD137/4-1BB, a TNFR family member is expressed on activated T cells as a co-stimulator. It transduces the signal for cell survival and differentiation and plays a crucial role in CD8 cytotoxic T cells. Recently, an increasing number of reports have indicated its important role on tumor immunity, and the studies of immunotherapy targeting CD137 are on going. Therefore, it is important to know the expression of CD137 and CD137L on malignant cells for the establishment of immunotherapy. As a first step, we examined CD137 expression on PBMCs from healthy donors and CLL patients. When PBMCs from healthy donors were stimulated with PMA and ionomycin, CD137 expression was induced not only on T cells but also on activated B cells. However, when PBMCs from CLL patients were stimulated in the same way, we could not detect CD137 induction on CLL B cells. Since more than 90% of lymphocytes in the patients were CLL B cells, it is conceivable that activated T cells were required to induce CD137 on B cells. To test this hypothesis we next co-cultured CLL cells with T cells activated with anti-CD3/CD28 antibody-coated beads. In this co-culture CD137 was induced on CLL B cells, and this induction was diminished by anti-CD154 blocking antibody. Furthermore, CD137 was inducibly expressed on CLL B cells after co-culture with HeLa cells transfected with CD154 gene. The induction of CD137 mRNA was also clearly detected by RT-PCR after this stimulation. This CD137 induction was more significantly observed on CLL B cells (n=14, MFIR 11.5±6.9) as compared with B cells from healthy donors (n=4, MFIR 3.7±0.6, p=0.001) or non-CLL B cell malignancies (n=9, MFIR 4.2±3.43, p=0.003). Stimulation of CD137 expressed on BJAB transfectants by co-culture with CD137L-transfected CHO cells induced a conspicuous nuclear translocation of p52, a non-canonical NF-κB factor. In agreement with this activation, the expression of survival factor BCL-XL was upregulated. Consequently, the CD137 signal augmented the survival of CD154 stimulated CLL B cells in vitro. CD40 ligation can induce anti-CLL immunity and reduce CLL cells clinically. These data suggest that the inducibly expressed CD137 may diminish the effectiveness. It is possible that the fine adjustment of these co-stimulators can lead more effective immunotherapy. Disclosures No relevant conflicts of interest to declare.

Clonality and Phenotype in Spleens From Patients with Primary Immune Thrombocytopenia,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3291-3291
Author(s):  
Elena Sabattini ◽  
Pier Paolo Piccaluga ◽  
Claudia Mannu ◽  
Anna Candoni ◽  
Anna Gazzola ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Thrombocytopenia ◽  
Immune Modulation ◽  
Conflicts Of Interest ◽  
Granzyme B ◽  
White Pulp ◽  
Reaction Products ◽  
Gaussian Peak ◽  
Primary Immune Thrombocytopenia ◽  
Red Pulp

Abstract Abstract 3291 Primary immune thrombocytopenia (PIT) results from both increased platelet destruction and insufficient platelet production. Although the development of autoantibodies against platelet glycoproteins remains central in the pathophysiology of PIT, several abnormalities in the immune modulation system have been identified (Blood 2008 Aug 15;112(4):1147; Hematol Oncol Clin North Am. 2009 Dec;23(6):1177; Hum Immunol. 2010 Jun;71(6):586); We analysed morphology, lymphocyte phenotype and heavy immunoglobulin (IgH) and TCR gamma (TCRg) gene rearrangements in spleens from 31 PIT patients to assess possible impact on diagnosis and course, in comparison with 19 spleens surgically removed for trauma. Age ranged from 15 to 68 (mean 41.61y) with M/F of 9/22 in PIT and 18 to 89 (mean: 66y) with M/F 11/8 in controls. All PIT patients experienced at least one line therapy before surgery and 4 underwent anti-CD20 immunotherapy. Immunohistochemistry for CD3, CD20, CD4, CD8, CD56, CD57, PD1, Tia1, Granzyme B, FoxP3, CD72 was made in all cases; both IgH and TCRg gene analysis were possible in 24/31 PIT and 17/19 controls, while 4/31 PIT and 2/19 controls were examined for either one (PIT: 2 TCR and 2 IgH, controls 1 TCR and 1 IgH) and 5 PIT and 1 control were excluded for unsatisfactory material. Ay histology all cases but 2 showed expanded white pulp (that was hypoplastic in the 2/4 cases that underwent Rituximab before surgery), moderate lymphocytic and modest granulocytic infiltrates in the red pulp; haemorragic lakes were present in control spleens. Immunohistochemistry showed similar stains in the 2 groups with normal distribution (white pulp: CD20+ B follicles, CD72-+ in the marginal zone, CD3+/CD4+ T cells, PD1/CD57+ T cells in the germinal centers; red pulp: regular CD20/CD3 and CD4/CD8 ratio, PD1/Tia1/Granzyme B expressed in roughly less than 20% CD3+ T cells; scattered CD57+/CD56- T cells. For molecular results see table 1 below. Monoclonality was defined if 1 or 2 peaks of amplified polymerase chain reaction products were obtained, oligoclonality with 3 to 5 peaks and polyclonality with a Gaussian peak distribution.Table 1IGHWDCtrlIGHWDCtrlPoly2015Poly-Oligo2116Oligo10Mono32Mono32TCRWDCtrlTCRWDCtrlPoly75Poly-Oligo128Oligo53Mono129Mono129 The results showed no statistically significant differences between PIT and controls as for morphology, phenotype and clonality. Since a decrease in regulatory T cells (T regs) is reported in PIT among other immune-impairments (Eur J Haematol. 2007 Oct;79(4):310; Zhonghua Nei Ke Za Zhi. 2010 Mar;49(3):213;Blood. 2009 Mar 12;113(11):256) we immunostained all cases with T reg-related nuclear molecule Foxp3: in control cases few cells in the white and red pulp were observed, while in PIT spleens fewer Foxp3 positive cells could only be seen in the red pulp: although results are slightly different, the low amount of positive cells in both groups decreases the reliable reproducibility of such observation. Moreover, the use of glucocorticoids by all patients before splenectomy, could have further reduced (Eur J Haematol. 2007 Oct;79(4):310) T regs levels. Overlapping molecular results were also obtained in the two groups in agreement with previous reports (Hematology. 2009 Aug;14(4):237; Platelets. 2009 Mar;20(2):135; Int J Hematol. 2003 Dec;78(5):461; Blood. 2002 Aug 15;100(4):1388). The attempt to translate the molecular findings into immunomorphologic differences between monoclonal and non monoclonal cases failed since neither amount/distribution of B and T cells nor T cell subtypes showed evident differences. On the whole, our results show that neither lymphoid phenotype nor IgH or TCRg clonality can be used as specific features of refractory PIT or guide treatment choice.Figure 1Figure 1. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Selective Induction of Th2-Attracting Chemokines CCL17 and CCL22 in Human B Cells by Latent Membrane Protein 1 of Epstein-Barr Virus

2004 ◽  
Vol 78 (4) ◽  
pp. 1665-1674 ◽  
Author(s):  
Takashi Nakayama ◽  
Kunio Hieshima ◽  
Daisuke Nagakubo ◽  
Emiko Sato ◽  
Masahiro Nakayama ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Regulatory T Cells ◽  
Epstein Barr Virus ◽  
Cytotoxic T Cells ◽  
Th2 Cells ◽  
Th1 Cells ◽  
Barr Virus ◽  
Ebv Infection ◽  
Epstein Barr

ABSTRACT Chemokines are likely to play important roles in the pathophysiology of diseases associated with Epstein-Barr virus (EBV). Here, we have analyzed the repertoire of chemokines expressed by EBV-infected B cells. EBV infection of B cells induced expression of TARC/CCL17 and MDC/CCL22, which are known to attract Th2 cells and regulatory T cells via CCR4, and also upregulated constitutive expression of MIP-1α/CCL3, MIP-1β/CCL4, and RANTES/CCL5, which are known to attract Th1 cells and cytotoxic T cells via CCR5. Accordingly, EBV-immortalized B cells secreted these chemokines, especially CCL3, CCL4, and CCL22, in large quantities. EBV infection or stable expression of LMP1 also induced CCL17 and CCL22 in a B-cell line, BJAB. The inhibitors of the TRAF/NF-κB pathway (BAY11-7082) and the p38/ATF2 pathway (SB202190) selectively suppressed the expression of CCL17 and CCL22 in EBV-immortalized B cells and BJAB-LMP1. Consistently, transient-transfection assays using CCL22 promoter-reporter constructs demonstrated that two NF-κB sites and a single AP-1 site were involved in the activation of the CCL22 promoter by LMP1. Finally, serum CCL22 levels were significantly elevated in infectious mononucleosis. Collectively, LMP1 induces CCL17 and CCL22 in EBV-infected B cells via activation of NF-κB and probably ATF2. Production of CCL17 and CCL22, which attract Th2 and regulatory T cells, may help EBV-infected B cells evade immune surveillance by Th1 cells. However, the concomitant production of CCL3, CCL4, and CCL5 by EBV-infected B cells may eventually attract Th1 cells and cytotoxic T cells, leading to elimination of EBV-infected B cells at latency III and to selection of those with limited expression of latent genes.

scholarly journals P2.03-37 The Efficiency of Octamer-4 Specific Cytotoxic T Cells Induce By CD40-B Cells in Killing Lung Cancer Stem-Like Cells

2018 ◽  
Vol 13 (10) ◽  
pp. S730
Author(s):  
X. Zhang ◽  
J. Xu ◽  
F. Hu ◽  
H. Wang ◽  
X. Zheng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
B Cells ◽  
Cytotoxic T Cells

scholarly journals New insights in the biology of Hodgkin lymphoma

Hematology ◽  
2012 ◽  
Vol 2012 (1) ◽  
pp. 328-334 ◽  
Author(s):  
Ralf Küppers
Keyword(s):  
T Cells ◽  
B Cells ◽  
Signaling Pathways ◽  
Hodgkin Lymphoma ◽  
Tumor Cells ◽  
Cytotoxic T Cells ◽  
Cell Gene Expression ◽  
Expression Program ◽  
Multiple Signaling ◽  
Cell Gene

Abstract The Hodgkin and Reed/Sternberg (HRS) tumor cells of classical Hodgkin lymphoma (HL) and the lymphocyte-predominant tumor cells of nodular lymphocyte–predominant HL are both derived from germinal center B cells. HRS cells, however, have largely lost their B-cell gene-expression program and coexpress genes typical of various types of hematopoietic cells. Multiple signaling pathways show a deregulated activity in HRS cells. The genetic lesions involved in the pathogenesis of HL are only partly known, but numerous members and regulators of the NF-κB and JAK/STAT signaling pathways are affected, suggesting an important role for these pathways in HL pathogenesis. Some genetic lesions involve epigenetic regulators, and there is emerging evidence that HRS cells have undergone extensive epigenetic alterations compared with normal B cells. HRS and lymphocyte-predominant cells are usually rare in the lymphoma tissue, and interactions with other cells in the microenvironment are likely critical for HL pathophysiology. T cells represent a main population of infiltrating cells, and it appears that HRS cells both inhibit cytotoxic T cells efficiently and also receive survival signals from Th cells in direct contact with them.

scholarly journals Human macrophage inflammatory protein alpha (MIP-1 alpha) and MIP-1 beta chemokines attract distinct populations of lymphocytes.

1993 ◽  
Vol 177 (6) ◽  
pp. 1821-1826 ◽  
Author(s):  
T J Schall ◽  
K Bacon ◽  
R D Camp ◽  
J W Kaspari ◽  
D V Goeddel
Keyword(s):  
T Cells ◽  
B Cells ◽  
Cytotoxic T Cells ◽  
Human Macrophage ◽  
Immune Effector ◽  
Effector Cells ◽  
Inflammatory Protein ◽  
And Migration ◽  
Macrophage Inflammatory Protein

Lymphocyte trafficking is an essential process in immune and inflammatory functions which can be thought to contain at least two main components: adhesion and migration. Whereas adhesion molecules such as the selections are known to mediate the homing of leukocytes from the blood to the endothelium, the chemoattractant substances responsible for the migration of specific subsets of lymphocytes to sites of infection or inflammation are largely unknown. Here we show that two molecules in the chemokine (for chemoattractant cytokine) superfamily, human macrophage inflammatory protein 1 alpha (MIP-1 alpha) and MIP-1 beta, do not share identical attractant activities for lymphocyte subpopulations. When analyzed in vitro in microchemotaxis experiments, HuMIP-1 beta tends to attract CD4+ T lymphocytes, with some preference for T cells of the naive (CD45RA) phenotype. HuMIP-1 alpha, when tested in parallel with HuMIP-1 beta, is a more potent lymphocyte chemoattractant with a broader range of concentration-dependent chemoattractant specificities. HuMIP-1 alpha at a concentration of 100 pg/ml attracts B cells and cytotoxic T cells, whereas at higher concentrations (10 ng/ml), the migration of these cells appears diminished, and the migration of CD4+ T cells is enhanced. Thus, in this assay system, HuMIP-1 alpha and -1 beta have differential attractant activities for subsets of immune effector cells, with HuMIP-1 alpha having greater effects than HuMIP-1 beta, particularly on B cells.

T- and B-Lymphocyte Subsets in Patients with Dupuytren’s Disease

1998 ◽  
Vol 23 (6) ◽  
pp. 724-727 ◽  
Author(s):  
K. G. GUDMUNDSSON ◽  
R. ARNGRÍMSSON ◽  
S. ARINBJARNARSON ◽  
A. OLAFSSON ◽  
T. JONSSON
Keyword(s):  
T Cells ◽  
B Cells ◽  
B Lymphocyte ◽  
Lymphocyte Subsets ◽  
Autoimmune Disorder ◽  
Dupuytren’S Disease ◽  
Control Group ◽  
Activated T Cells ◽  
Dupuytren's Disease ◽  
Immunological Mechanisms

Previous reports have indicated that inflammatory mechanisms may be involved in the pathogenesis of Dupuytren’s disease and it has even been suggested that this condition is a T-cell mediated autoimmune disorder. We investigated peripheral blood lymphocyte subsets from 21 patients with Dupuytren’s disease and compared them with ten healthy blood donors. The Dupuytren’s patients had an increase in DR+ T-cells compared with healthy controls. Furthermore, patients with both palmar and plantar involvement had a higher percentage of DR+ T-cells than those with only the palm affected. The percentage of circulating CD5+ B-cells was lower in the Dupuytren’s patients compared with the control group; this feature was marginally significant for the whole group of Dupuytren’s patients but was strongest in the group of patients with both palmar and plantar involvement. These findings support previous suggestions that immunological mechanisms, involving activated T-cells and probably also B-cells, are involved in the pathogenesis of Dupuytren’s disease.

scholarly journals Efficient Generation of Antigen-Specific Cytotoxic T Cells Using Retrovirally Transduced CD40-Activated B Cells

2002 ◽  
Vol 169 (4) ◽  
pp. 2164-2171 ◽  
Author(s):  
Eisei Kondo ◽  
Max S. Topp ◽  
Hans-Peter Kiem ◽  
Yuichi Obata ◽  
Yasuo Morishima ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Cytotoxic T Cells ◽  
Efficient Generation ◽  
Activated B Cells
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