scholarly journals Enhancement of thymopoiesis after bone marrow transplant by in vivo interleukin-7

Blood ◽  
1996 ◽  
Vol 88 (5) ◽  
pp. 1887-1894 ◽  
Author(s):  
E Bolotin ◽  
M Smogorzewska ◽  
S Smith ◽  
M Widmer ◽  
K Weinberg
Keyword(s):  
Immune Deficiency ◽  
Bone Marrow ◽  
T Lymphocytes ◽  
B Cell ◽  
Cell Function ◽  
Normal Numbers ◽  
B Cell Function ◽  
Interleukin 7 ◽  
Immature Thymocytes

Abstract Bone marrow transplantation (BMT) is followed by a period of profound immune deficiency, during which new T lymphocytes are generated from either stem cells or immature thymic progenitors. Interleukin-7 (IL-7) induces proliferation and differentiation of immature thymocytes. We examined whether the in vivo administration of IL-7 to mice receiving BMT would alter thymic reconstitution. Lethally irradiated C57BL/6 mice received syngeneic BMT, followed by either IL-7 or placebo from days 5 to 18 post-BMT. At day 28, BMT recipients that had not received IL-7 had profound thymic hypoplasia (< 5% of normal), with relative increases in the numbers of immature thymocytes, decreased numbers of mature peripheral (splenic) T lymphocytes, and severely impaired T- and B-cell function. In contrast, transplanted mice treated with IL-7 had normalization of thymic cellularity, with normal proportions of thymic subsets and T-cell receptor beta variable gene (TCRV beta) usage, normal numbers of peripheral CD4+ T lymphocytes, and improved antigen- specific T- and B-cell function. In the BMT-IL-7 mice, there was an eightfold increase in the number of immature CD3-CD4-CD8- thymocytes in G2-M of the cell cycle, indicating that restoration of thymic cellularity was due to enhanced proliferation of immature thymic progenitors. Similar effects following IL-7 administration were also observed when donor bone marrow was depleted of mature T lymphocytes, indicating that IL-7 administration affected immature hematopoietic progenitors. IL-7 promotes thymic reconstitution after BMT, and may be useful in preventing post-BMT immune deficiency.

scholarly journals Enhancement of thymopoiesis after bone marrow transplant by in vivo interleukin-7

Blood ◽  
1996 ◽  
Vol 88 (5) ◽  
pp. 1887-1894 ◽  
Author(s):  
E Bolotin ◽  
M Smogorzewska ◽  
S Smith ◽  
M Widmer ◽  
K Weinberg
Keyword(s):  
Immune Deficiency ◽  
Bone Marrow ◽  
T Lymphocytes ◽  
B Cell ◽  
Cell Function ◽  
Normal Numbers ◽  
B Cell Function ◽  
Interleukin 7 ◽  
Immature Thymocytes

Bone marrow transplantation (BMT) is followed by a period of profound immune deficiency, during which new T lymphocytes are generated from either stem cells or immature thymic progenitors. Interleukin-7 (IL-7) induces proliferation and differentiation of immature thymocytes. We examined whether the in vivo administration of IL-7 to mice receiving BMT would alter thymic reconstitution. Lethally irradiated C57BL/6 mice received syngeneic BMT, followed by either IL-7 or placebo from days 5 to 18 post-BMT. At day 28, BMT recipients that had not received IL-7 had profound thymic hypoplasia (< 5% of normal), with relative increases in the numbers of immature thymocytes, decreased numbers of mature peripheral (splenic) T lymphocytes, and severely impaired T- and B-cell function. In contrast, transplanted mice treated with IL-7 had normalization of thymic cellularity, with normal proportions of thymic subsets and T-cell receptor beta variable gene (TCRV beta) usage, normal numbers of peripheral CD4+ T lymphocytes, and improved antigen- specific T- and B-cell function. In the BMT-IL-7 mice, there was an eightfold increase in the number of immature CD3-CD4-CD8- thymocytes in G2-M of the cell cycle, indicating that restoration of thymic cellularity was due to enhanced proliferation of immature thymic progenitors. Similar effects following IL-7 administration were also observed when donor bone marrow was depleted of mature T lymphocytes, indicating that IL-7 administration affected immature hematopoietic progenitors. IL-7 promotes thymic reconstitution after BMT, and may be useful in preventing post-BMT immune deficiency.

scholarly journals Engagement of CD83 on B Cells Modulates B Cell Function In Vivo

2009 ◽  
Vol 182 (5) ◽  
pp. 2827-2834 ◽  
Author(s):  
Birte Kretschmer ◽  
Katja Lüthje ◽  
Stefanie Schneider ◽  
Bernhard Fleischer ◽  
Minka Breloer
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Function ◽  
B Cell Function

Long-Term Chimerism and B-Cell Function After Bone Marrow Transplantation in Patients With Severe Combined Immunodeficiency With B Cells: A Single-Center Study of 22 Patients

Blood ◽  
1999 ◽  
Vol 94 (8) ◽  
pp. 2923-2930 ◽  
Author(s):  
Elie Haddad ◽  
Françoise Le Deist ◽  
Pierre Aucouturier ◽  
Marina Cavazzana-Calvo ◽  
Stephane Blanche ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Bone Marrow Transplantation ◽  
B Cells ◽  
B Cell ◽  
Cell Function ◽  
Severe Combined Immunodeficiency ◽  
Combined Immunodeficiency ◽  
B Cell Function ◽  
Host Origin

We retrospectively analyzed the B-cell function and leukocyte chimerism of 22 patients with severe combined immunodeficiency with B cells (B+ SCID) who survived more than 2 years after bone marrow transplantation (BMT) to determine the possible consequences of BMT procedures, leukocyte chimerism, and SCID molecular deficit on B-cell function outcome. Circulating T cells were of donor origin in all patients. In recipients of HLA-identical BMT (n = 5), monocytes were of host origin in 5 and B cells were of host origin in 4 and of mixed origin in 1. In recipients of HLA haploidentical T-cell–depleted BMT (n = 17), B cells and monocytes were of host origin in 14 and of donor origin in 3. Engraftment of B cells was found to be associated with normal B-cell function. In contrast, 10 of 18 patients with host B cells still require Ig substitution. Conditioning regimen (ie, 8 mg/kg busulfan and 200 mg/kg cyclophosphamide) was shown neither to promote B-cell and monocyte engraftment nor to affect B-cell function. Eight patients with B cells of host origin had normal B-cell function. Evidence for functional host B cells was further provided in 3 informative cases by Ig allotype determination and by the detection, in 5 studied cases, of host CD27+ memory B cells as in age-matched controls. These results strongly suggest that, in some transplanted patients, host B cells can cooperate with donor T cells to fully mature in Ig-producing cells.

scholarly journals Immune reconstitution in severe combined immunodeficiency disease after lectin-treated, T-cell-depleted haplocompatible bone marrow transplantation

Blood ◽  
1993 ◽  
Vol 81 (8) ◽  
pp. 2021-2030 ◽  
Author(s):  
Y Dror ◽  
R Gallagher ◽  
DW Wara ◽  
BW Colombe ◽  
A Merino ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
B Cell ◽  
Cell Function ◽  
Severe Combined Immunodeficiency ◽  
Combined Immunodeficiency ◽  
Cell Numbers ◽  
B Cell Function ◽  
Immunodeficiency Disease ◽  
Severe Combined Immunodeficiency Disease

Abstract We describe our 9-year experience with lectin-treated T-cell-depleted haplocompatible parental bone marrow transplantation (BMT) for 24 patients with severe combined immunodeficiency disease (SCID). Nineteen of 21 evaluable patients had T-cell engraftment; 2 of 11 patients tested had B-cell and monocyte engraftment. Fourteen of 24 (58%) patients are alive 7 months to 9.8 years post-BMT. Seventeen of 24 patients received pretransplant conditioning with chemotherapy and/or total body irradiation, and 8 of 24 received more than one transplant. Patients who received conditioning had a survival rate of 61% versus 57% for those who received no conditioning. None received graft-versus- host disease (GVHD) prophylaxis and no patient had acute or chronic GVHD greater than grade I. Kinetics and follow-up of immune recovery were analyzed in 14 patients who are greater than 1 year from transplant. Half of the patients showed evidence of T-cell function by 3 months and normal T-cell function by 4 to 7 months post-BMT. On average, T-cell numbers and subsets became normal 10 to 12 months posttransplant. Recovery of B-cell function was more delayed, although in most patients B-cell numbers and IgM levels were normal by 12 months post-BMT. B-cell function, as determined by isohemagglutinin titers or specific antibodies to pneumococcal polysaccharide, keyhole limpet hemocyanin, or tetanus toxoid, became normal in 10 of 14 patients 2 to 8 years post-BMT. Seven of the 14 are off gammaglobulin therapy. Production of isohemagglutinins tended to predict recovery of antibody response to pneumococcal polysaccharide (P < .064). Based on these results, we believe that haplocompatible BMT is an effective, curative treatment for patients with SCID who lack an HLA-matched related donor.

Deficiencies of Innate and Adaptive Immunity

2013 ◽  
Author(s):  
Kathleen E Sullivan ◽  
Soma Jyonouchi
Keyword(s):  
Immune Deficiency ◽  
Innate Immunity ◽  
T Cell ◽  
B Cell ◽  
Signaling Pathway ◽  
Interferon Gamma ◽  
Cell Function ◽  
Tlr Signaling ◽  
Immunoglobulin Production ◽  
B Cell Function

Defects in B cell function, T cell function, and innate immunity comprise the majority of primary immune deficiencies. Each compartment has a characteristic set of archetypical features. Defects in B cell function are characterized by poor immunoglobulin production, which, in turn, leads to recurrent sinopulmonary infections. Defects in T cell function are characterized by delayed clearance of viruses, susceptibility to opportunistic infections, and a high rate of autoimmune disease. Defects of innate immunity are typically associated with early-onset, severe infections. This chapter describes defects in immunoglobulin production or function, T cell disorders, defects in Toll-like receptor (TLR) signaling, defects in the interleukin-12 (IL-12)/interferon-gamma signaling pathway, and defects of T helper type 17 (Th17) immunity. Tables outline specific pathogens that should alert the clinician to potential immune deficiency, provide a comparison of immunoglobulin production defects, and describe severe combined immune deficiency types. Figures include schematic representations of the TLR signaling pathway, the IL-12/interferon-gamma signaling pathway, and the Th17 immune response. This chapter contains 3 highly rendered figures, 3 tables, 72 references, and 5 MCQs.

scholarly journals Raloxifene- and estradiol-mediated effects on uterus, bone and B lymphocytes in mice

2002 ◽  
Vol 175 (2) ◽  
pp. 319-327 ◽  
Author(s):  
MC Erlandsson ◽  
CA Jonsson ◽  
MK Lindberg ◽  
C Ohlsson ◽  
H Carlsten
Keyword(s):  
Bone Marrow ◽  
Estrogen Receptor ◽  
B Cell ◽  
Cell Function ◽  
Quantitative Computed Tomography ◽  
B Lymphopoiesis ◽  
Uterine Tissue ◽  
Mineral Density ◽  
B Cell Function ◽  
Mediated Effects

Raloxifene is a selective estrogen receptor modulator approved for the prevention of osteoporosis in postmenopausal women. It is selective by having estrogen-agonistic effects on bone, vessels and blood lipids while it is antagonistic on mammary and uterine tissue. Our aim was to study the agonistic and antagonistic properties of the raloxifene analogue LY117018 (LY) on uterus, bone, B lymphopoiesis and B cell function. Oophorectomized and sham-operated animals were treated with s.c. injections of equipotent anti-osteoporotic doses of 17beta-estradiol (E2) (0.1 mg/kg) or LY (3 mg/kg) or vehicle as controls. Effects on bone mineral density (BMD) were studied using peripheral quantitative computed tomography, uterine weight was examined, B lymphopoiesis was examined using flow cytometry and B cell function in bone marrow and spleen was studied by the use of an ELISPOT assay. E2 and LY had similar effects on BMD and bone marrow B lymphopoiesis, while LY had a clear antagonistic effect on endogenous estrogen in uterine tissue and no stimulating effect on the frequency of Ig-producing B cells in sham-operated animals. Our results are discussed in the context of estrogen receptor biology, relations between the immune system and bone metabolism and also with respect to the estrogen-mediated effects on rheumatic diseases.

In vivo versus in vitro assays for assessment of T- and B- cell function

1994 ◽  
Vol 6 (2) ◽  
pp. 320-326 ◽  
Author(s):  
Martin F. Bachmann ◽  
Thomas M. Kündig
Keyword(s):  
B Cell ◽  
Cell Function ◽  
In Vitro Assays ◽  
B Cell Function

scholarly journals Immune reconstitution in severe combined immunodeficiency disease after lectin-treated, T-cell-depleted haplocompatible bone marrow transplantation

Blood ◽  
1993 ◽  
Vol 81 (8) ◽  
pp. 2021-2030 ◽  
Author(s):  
Y Dror ◽  
R Gallagher ◽  
DW Wara ◽  
BW Colombe ◽  
A Merino ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
B Cell ◽  
Cell Function ◽  
Severe Combined Immunodeficiency ◽  
Combined Immunodeficiency ◽  
Cell Numbers ◽  
B Cell Function ◽  
Immunodeficiency Disease ◽  
Severe Combined Immunodeficiency Disease

We describe our 9-year experience with lectin-treated T-cell-depleted haplocompatible parental bone marrow transplantation (BMT) for 24 patients with severe combined immunodeficiency disease (SCID). Nineteen of 21 evaluable patients had T-cell engraftment; 2 of 11 patients tested had B-cell and monocyte engraftment. Fourteen of 24 (58%) patients are alive 7 months to 9.8 years post-BMT. Seventeen of 24 patients received pretransplant conditioning with chemotherapy and/or total body irradiation, and 8 of 24 received more than one transplant. Patients who received conditioning had a survival rate of 61% versus 57% for those who received no conditioning. None received graft-versus- host disease (GVHD) prophylaxis and no patient had acute or chronic GVHD greater than grade I. Kinetics and follow-up of immune recovery were analyzed in 14 patients who are greater than 1 year from transplant. Half of the patients showed evidence of T-cell function by 3 months and normal T-cell function by 4 to 7 months post-BMT. On average, T-cell numbers and subsets became normal 10 to 12 months posttransplant. Recovery of B-cell function was more delayed, although in most patients B-cell numbers and IgM levels were normal by 12 months post-BMT. B-cell function, as determined by isohemagglutinin titers or specific antibodies to pneumococcal polysaccharide, keyhole limpet hemocyanin, or tetanus toxoid, became normal in 10 of 14 patients 2 to 8 years post-BMT. Seven of the 14 are off gammaglobulin therapy. Production of isohemagglutinins tended to predict recovery of antibody response to pneumococcal polysaccharide (P < .064). Based on these results, we believe that haplocompatible BMT is an effective, curative treatment for patients with SCID who lack an HLA-matched related donor.

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