Signals controlling rest and reactivation of T helper memory lymphocytes in bone marrow

2012 ◽  
Vol 69 (10) ◽  
pp. 1609-1613 ◽  
Author(s):  
Koji Tokoyoda ◽  
Andreas Radbruch
Keyword(s):  
Bone Marrow ◽  
T Helper ◽  
Memory Lymphocytes

scholarly journals Dendritic cells mediate the induction of polyfunctional human IL17-producing cells (Th17-1 cells) enriched in the bone marrow of patients with myeloma

Blood ◽  
2008 ◽  
Vol 112 (7) ◽  
pp. 2878-2885 ◽  
Author(s):  
Kavita M. Dhodapkar ◽  
Scott Barbuto ◽  
Phillip Matthews ◽  
Anjli Kukreja ◽  
Amitabha Mazumder ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
Th17 Cells ◽  
T Helper ◽  
Tumor Bed ◽  
Distinct Lineage ◽  
Human Dendritic Cells ◽  
Antigen Presenting ◽  
Dc Maturation

Abstract IL17-producing (Th17) cells are a distinct lineage of T helper cells that regulate immunity and inflammation. The role of antigen-presenting cells in the induction of Th17 cells in humans remains to be fully defined. Here, we show that human dendritic cells (DCs) are efficient inducers of Th17 cells in culture, including antigen-specific Th17 cells. Although most freshly isolated circulating human Th17 cells secrete IL17 alone or with IL2, those induced by DCs are polyfunctional and coexpress IL17 and IFNγ (Th17-1 cells). The capacity of DCs to expand Th17-1 cells is enhanced upon DC maturation, and mature DCs are superior to monocytes for the expansion of autologous Th17 cells. In myeloma, where tumors are infiltrated by DCs, Th17 cells are enriched in the bone marrow relative to circulation. Bone marrow from patients with myeloma contains a higher proportion of Th17-1 cells compared with the marrow in preneoplastic gammopathy (monoclonal gammopathy of undetermined significance [MGUS]). Uptake of apoptotic but not necrotic myeloma tumor cells by DCs leads to enhanced induction of Th17-1 cells. These data demonstrate the capacity of DCs to induce expansion of polyfunctional IL17-producing T cells in humans, and suggest a role for DCs in the enrichment of Th17-1 cells in the tumor bed.

scholarly journals Imbalances within the peripheral blood T-helper (CD4+) and T-suppressor (CD8+) cell populations in the reconstitution phase after human bone marrow transplantation

Blood ◽  
1988 ◽  
Vol 71 (5) ◽  
pp. 1196-1200 ◽  
Author(s):  
A Velardi ◽  
A Terenzi ◽  
S Cucciaioni ◽  
R Millo ◽  
CE Grossi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Bone Marrow Transplantation ◽  
T Cell ◽  
Peripheral Blood ◽  
Marrow Transplantation ◽  
Allogeneic Bone Marrow Transplantation ◽  
T Cell Subsets ◽  
Allogeneic Bone ◽  
T Helper

Abstract Peripheral blood T cell subsets were evaluated in 11 patients during the reconstitution phase after allogeneic bone marrow transplantation and compared with 11 age-matched controls. The proportion of cells coexpressing Leu7 and CD11b (C3bi receptor) markers was determined within the CD4+ (T-helper) and the CD8+ (T-suppressor) subsets by two- color immunofluorescence analysis. CD4+ and CD8+ T cells reached normal or near-normal values within the first year posttransplant. In contrast to normal controls, however, most of the cells in both subsets coexpressed the Leu7 and CD11b markers. T cells with such phenotype display the morphological features of granular lymphocytes (GLs) and a functional inability to produce interleukin 2 (IL 2). These T cell imbalances were not related to graft v host disease (GvHD) or to clinically detectable virus infections and may account for some defects of cellular and humoral immunity that occur after bone marrow transplantation./

Subsets and Function Changes of Th Cells in the Bone Marrow of Patients with Immune Related Pancytopenia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3762-3762
Author(s):  
Guangsheng He ◽  
Xiuli Wang ◽  
De Pei Wu ◽  
Aining Sun ◽  
Zhengming Jin
Keyword(s):  
Bone Marrow ◽  
Mononuclear Cells ◽  
Th2 Cells ◽  
Th1 Cells ◽  
T Helper ◽  
Ifn Γ ◽  
Polymerase Chain ◽  
And Function ◽  
Normal Controls ◽  
Th Lymphocytes

Abstract Objectives To explore the subsets and function of T helper (Th) in bone marrow of the patients with immune related pancytopenia(IRP). Methods The CD4+ cells producing IFN-γ or IL-4 in cytoplasm were defined as Th1 or Th2 cells respectively. All these cells in bone marrow were measured from 16 normal controls, 25 untreated IRP patients; The mRNA expressions of IL-4, IL-10, IFN-γ and IL-2 genes in unstimulated bone marrow mononuclear cells(BMMNC)from 25 untreated IRP patients, 10 normal controls were measured by reverse transcription polymerase chain reaction (RT-PCR). Results The percentage of Th1 cells, Th2 cells and ratio of Th1/Th2 in bone marrow of normal controls was: 0.42%, 0.24%, 1.57 respectively, and the percentage of Th1 cells in untreated patients with IRP was 0.58%, which was not markedly different from the that of normal controls(t=0.903, P>0.05). But the percentage of Th2 cells of the patients with IRP was significantly higher than that of normal controls(t=4.673, P<0.01), and the balance of Th1/Th2 shifted to Th2 more significantly by comparing to that of normal controls (t=4.880, P<0.01). The mRNA expressions of IL-4 and IL-10 in the Th2 cells of the untreated IRP patients were significantly higher than those of the normal controls, however difference of the expressions of IFN-γ and IL-2 in the Th1 cells were not significantly. Conclusions The percentage of Th2 cells increased in the patients with IRP, and the balance of Th1/Th2 shifted to Th2. And the expression of Th2 type cytokines was more frequent in IRP. The imbalance of subtypes of Th lymphocytes and hyperfunction of Th2 lymphocytes might play important roles in the pathogenic mechanism of IRP, which lead to more B lymphocytes and producing autoantibodies consistenly.

scholarly journals Restricted helper function of F1 leads to parent bone marrow chimeras controlled by K-end of H-2 complex.

1978 ◽  
Vol 147 (6) ◽  
pp. 1838-1842 ◽  
Author(s):  
J Sprent
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
T Cells ◽  
B Cells ◽  
Parental Strain ◽  
T Helper ◽  
F1 Hybrid ◽  
Active Suppression ◽  
Helper Function ◽  
Bone Marrow Chimeras

F1 leads to parent bone marrow chimeras were prepared by transferring F1 hybrid marrow cells into heavily irradiated parental strain mice. When unprimed, donor-derived F1 T cells from the chimeras were activated to sheep erythrocytes (SRC) for 5 days in irradiated normal F1 mice, high IgM and IgG anti-SRC responses were observed with F1 B cells, and with B cells H-2-compatible with the strain in which the T cells were raised from stem cells. Significantly, however, responses with B cells of the opposite parental strain were either absent or very low. The restriction in T-helper function mapped to the K-end of the H-2 complex and could not be attributed to active suppression.

Defective antifungal T-helper 1 (TH1) immunity in a murine model of allogeneic T-cell–depleted bone marrow transplantation and its restoration by treatment with TH2 cytokine antagonists

Blood ◽  
2001 ◽  
Vol 97 (5) ◽  
pp. 1483-1490 ◽  
Author(s):  
Antonella Mencacci ◽  
Katia Perruccio ◽  
Angela Bacci ◽  
Elio Cenci ◽  
Roberta Benedetti ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
Fungal Infections ◽  
Th2 Cytokines ◽  
T Helper ◽  
T Helper 1 ◽  
Cytokine Antagonists ◽  
Th2 Cytokine ◽  
Donor Type ◽  
Th1 Cytokines

Patients undergoing full haplotype-mismatched hematopoietic transplantations may experience severe intractable invasive fungal infections. To verify whether an imbalanced production of T-helper 1 (TH1) and TH2 cytokines may be responsible for susceptibility to fungal infections, C3H/HeJ (H-2k) recipient mice were lethally irradiated, received transplantations with T-cell–depleted allogeneic bone marrow (BM) cells from mice ofH-2d haplotype, and were infected withCandida albicans. At different time-points after transplantation, mice were assessed for pattern of TH cytokine production and susceptibility to infection. The results show that a long-term, donor-type chimerism was achieved as early as 2 weeks after BM transplantation (BMT), at the time when high-level production of TH2 cytokines (interleukin-4 [IL-4] and IL-10) and impaired production of TH1 cytokines (interferon-γ [IFN-γ] and IL-12] were observed. At this time, mice were highly susceptible to both disseminated and mucosal infections, as indicated by decreased survival, uncontrolled fungal growth, and failure to develop protective TH1 immunity. However, a predominant production of TH1 cytokines was observed by week 5 after BMT, at the time when mice developed donor-type protective TH1 responses and were resistant to infections. Therapeutic ablation of IL-4 or IL-10 greatly increased resistance to candidiasis. These results indicate that a dysregulated production of TH cytokines occurs in mice undergoing T-cell–depleted allogeneic BMT. The transient predominant production of TH2 cytokines over that of IL-12 impaired the ability of mice to develop antifungal TH1 resistance, an activity that could be efficiently restored upon treatment with TH2 cytokine antagonists.

Bone Marrow Specimens From Patients with Immune Thrombocytopenia (ITP) Demonstrate Increased Megakaryocyte-Bound IgG and Increased T-Helper Cells

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2233-2233
Author(s):  
Lisa J. Toltl ◽  
Catherine Ross ◽  
John G. Kelton ◽  
Donald M. Arnold
Keyword(s):  
Bone Marrow ◽  
Platelet Count ◽  
Bone Marrow Biopsy ◽  
T Helper Cells ◽  
Research Funding ◽  
Immune Thrombocytopenia ◽  
T Helper ◽  
Hematopoietic Growth Factors ◽  
Cell Numbers ◽  
Igg Binding

Abstract Abstract 2233 BACKGROUND: Immune thrombocytopenia (ITP) is a heterogeneous autoimmune disease characterized by low platelet counts and platelet autoantibodies. The mechanisms of ITP remain unclear although recent evidence suggests that megakaryocytes may be the target of immune destruction. To test this hypothesis we evaluated IgG-binding to megakaryocytes and B- and T-cells in bone marrow specimens of ITP patients and non-thrombocytopenic controls. METHODS: Histological slides of bone marrow biopsies from ITP patients and control patients were prepared from stored paraffin-embedded tissue blocks for blinded pathological assessment. Adult ITP patients (N=19) had a platelet count less than 100 x109/L (range 2 – 76 x109/L) as measured within 4 weeks before the date of bone marrow biopsy procurement without splenomegaly, myelodysplastic syndrome, lymphoproliferative disease, HIV, hepatitis B or C, drug-induced thrombocytopenia or prior treatment with thrombopoietin receptor agonists or other hematopoietic growth factors. Control patients (N=15) were adults with limited stage lymphoma or monoclonal gammopathy of undetermined significance with a normal platelet count (150 – 400 x109/L) who had a bone marrow biopsy for staging purposes which was reported as normal. Patients with prior use of anti-neoplastic agents or hematopoietic growth factors were excluded. Coded bone marrow biopsy sections were labeled with rabbit polyclonal anti-IgG, anti-CD4, anti-CD8, anti-CD20, and CD61 in serial sections, followed by streptavidin-biotin labeling techniques. The intensity of staining was assessed semi-quantitatively by an experienced hematopathologist for megakaryocyte, B-cell and T-cell numbers (increased, decreased, within normal limits) and megakaryocyte-bound IgG (negative, below 50% of cells positive or more than 50% of cells positive) blinded to diagnosis and platelet count. RESULTS: ITP bone marrows demonstrated greater IgG binding to megakaryocytes compared with controls [12/19 (63.16%) vs. 4/15 (26.67%), p=0.02], increased CD4+ cells [15/19 (78.95%) vs. 5/15 (33.33%), p=0.003] and marginally increased CD8+ cells [11/19 (57.89%) vs. 4/15 (26.67%), p=0.05]. B-cell numbers were not different between groups. CONCLUSIONS: Using bone marrow specimens from carefully selected ITP patients and controls, our study shows that IgG-bound megakaryocytes and T cells, especially T-helper cells, are increased in bone marrow of ITP patients compared with controls. These data provide evidence of megakaryocyte injury in ITP. Additional labeling with caspase-3 and TUNEL stains is planned to identify markers of apoptosis. Disclosures: Kelton: Amgen: Honoraria, Research Funding; GlaxoSmithKline: Honoraria, Research Funding. Arnold:Amgen: Honoraria, Research Funding; GlaxoSmithKline: Honoraria, Research Funding; Talecris: Honoraria; Hoffmann-LaRoche: Research Funding.

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