scholarly journals Transplantation for severe combined immunodeficiency with HLA-A,B,D,DR incompatible parental marrow cells fractionated by soybean agglutinin and sheep red blood cells

Blood ◽  
1983 ◽  
Vol 61 (2) ◽  
pp. 341-348 ◽  
Author(s):  
Y Reisner ◽  
N Kapoor ◽  
D Kirkpatrick ◽  
MS Pollack ◽  
S Cunningham-Rundles ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Blood Cells ◽  
Severe Combined Immunodeficiency ◽  
Cell Mediated Immunity ◽  
Combined Immunodeficiency ◽  
Soybean Agglutinin ◽  
Graft Versus Host ◽  
The Third ◽  
Immunologic Reconstitution ◽  
Marrow Cells

Abstract Three patients with severe combined immunodeficiency (SCID) received transplants of HLA haplotype-mismatched parental bone marrow depleted of T lymphocytes by differential agglutination with soybean agglutinin (SBA) and subsequent E-rosette depletion. Two patients achieved durable engraftment with reconstitution of both humoral and cell-mediated immunity. Neither of these patients developed graft versus host disease (GVHD). The third patient achieved only a transient engraftment with concomitant development of mitogen-responsive lymphocytes of paternal origin. Our experience indicates that depletion of T lymphocytes by this technique can abrogate the potential of histoincompatible marrow grafts to induce lethal GVHD without limiting immunologic reconstitution. It also provides further evidence of nonimmune mechanisms of graft resistance that may necessitate preparative treatment of patients with SCID before transplantation with HLA- mismatched marrow cells.

scholarly journals Transplantation for severe combined immunodeficiency with HLA-A,B,D,DR incompatible parental marrow cells fractionated by soybean agglutinin and sheep red blood cells

Blood ◽  
1983 ◽  
Vol 61 (2) ◽  
pp. 341-348 ◽  
Author(s):  
Y Reisner ◽  
N Kapoor ◽  
D Kirkpatrick ◽  
MS Pollack ◽  
S Cunningham-Rundles ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Blood Cells ◽  
Severe Combined Immunodeficiency ◽  
Cell Mediated Immunity ◽  
Combined Immunodeficiency ◽  
Soybean Agglutinin ◽  
Graft Versus Host ◽  
The Third ◽  
Immunologic Reconstitution ◽  
Marrow Cells

Three patients with severe combined immunodeficiency (SCID) received transplants of HLA haplotype-mismatched parental bone marrow depleted of T lymphocytes by differential agglutination with soybean agglutinin (SBA) and subsequent E-rosette depletion. Two patients achieved durable engraftment with reconstitution of both humoral and cell-mediated immunity. Neither of these patients developed graft versus host disease (GVHD). The third patient achieved only a transient engraftment with concomitant development of mitogen-responsive lymphocytes of paternal origin. Our experience indicates that depletion of T lymphocytes by this technique can abrogate the potential of histoincompatible marrow grafts to induce lethal GVHD without limiting immunologic reconstitution. It also provides further evidence of nonimmune mechanisms of graft resistance that may necessitate preparative treatment of patients with SCID before transplantation with HLA- mismatched marrow cells.

scholarly journals HLA-haploidentical bone marrow transplantation for severe combined immunodeficiency using E rosette fractionation and cyclosporine

Blood ◽  
1986 ◽  
Vol 67 (2) ◽  
pp. 444-449 ◽  
Author(s):  
A Fischer ◽  
A Durandy ◽  
JP de Villartay ◽  
E Vilmer ◽  
F Le Deist ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
T Lymphocytes ◽  
Marrow Transplantation ◽  
Bone Marrow Cells ◽  
Severe Combined Immunodeficiency ◽  
Cell Mediated Immunity ◽  
Continuous Intravenous Infusion ◽  
Combined Immunodeficiency ◽  
Lymphoproliferative Syndrome

Abstract Eight patients with severe combined immunodeficiency received bone marrow cells from their HLA haplotype-identical fathers after bone marrow T cell depletion by rosetting with neuraminidase-treated sheep red cells. Because the method led to the infusion of a small percentage of T lymphocytes (0.1% to 0.3%), cyclosporin was given by continuous intravenous infusion for two months in order to prevent the occurrence of graft-v-host disease (GVHD). Three patients who did have residual nonfunctional T lymphocytes received busulfan and cyclophosphamide before transplantation. Engraftment was observed in seven patients, and severe GVHD was not seen. Two patients died early after the bone marrow transplantation because of prior infections, and a third died at day 90 from a B cell lymphoproliferative syndrome. The five other patients are doing well. Stable engraftment has been achieved with reconstitution of cell-mediated immunity in 5/5 and humoral immunity in 4/5 patients.

scholarly journals HLA-haploidentical bone marrow transplantation for severe combined immunodeficiency using E rosette fractionation and cyclosporine

Blood ◽  
1986 ◽  
Vol 67 (2) ◽  
pp. 444-449 ◽  
Author(s):  
A Fischer ◽  
A Durandy ◽  
JP de Villartay ◽  
E Vilmer ◽  
F Le Deist ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
T Lymphocytes ◽  
Marrow Transplantation ◽  
Bone Marrow Cells ◽  
Severe Combined Immunodeficiency ◽  
Cell Mediated Immunity ◽  
Continuous Intravenous Infusion ◽  
Combined Immunodeficiency ◽  
Lymphoproliferative Syndrome

Eight patients with severe combined immunodeficiency received bone marrow cells from their HLA haplotype-identical fathers after bone marrow T cell depletion by rosetting with neuraminidase-treated sheep red cells. Because the method led to the infusion of a small percentage of T lymphocytes (0.1% to 0.3%), cyclosporin was given by continuous intravenous infusion for two months in order to prevent the occurrence of graft-v-host disease (GVHD). Three patients who did have residual nonfunctional T lymphocytes received busulfan and cyclophosphamide before transplantation. Engraftment was observed in seven patients, and severe GVHD was not seen. Two patients died early after the bone marrow transplantation because of prior infections, and a third died at day 90 from a B cell lymphoproliferative syndrome. The five other patients are doing well. Stable engraftment has been achieved with reconstitution of cell-mediated immunity in 5/5 and humoral immunity in 4/5 patients.

scholarly journals Development of Autologous, Oligoclonal, Poorly Functioning T Lymphocytes in a Patient With Autosomal Recessive Severe Combined Immunodeficiency Caused by Defects of the Jak3 Tyrosine Kinase

Blood ◽  
1998 ◽  
Vol 91 (3) ◽  
pp. 949-955 ◽  
Author(s):  
Duilio Brugnoni ◽  
Luigi D. Notarangelo ◽  
Alessandra Sottini ◽  
Paolo Airò ◽  
Marta Pennacchio ◽  
...  
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Tyrosine Kinase ◽  
Cd4 T Cells ◽  
Severe Combined Immunodeficiency ◽  
Combined Immunodeficiency ◽  
T Helper ◽  
T Helper 1 ◽  
In Vitro Susceptibility ◽  
And Function

Abstract Defects of the common gamma chain subunit of the cytokine receptors (γc) or of Jak3, a tyrosine kinase required for γc signal transduction, result in T−B+ severe combined immunodeficiency (SCID). However, atypical cases, characterized by progressive development of T lymphocytes, have been also reported. We describe a child with SCID caused by Jak3 gene defects, which strongly but not completely affect Jak3 protein expression and function, who developed a substantial number (>3,000/μL) of autologous CD3+CD4+ T cells. These cells showed a primed/activated phenotype (CD45R0+ Fas+HLA-DR+ CD62Llo), defective secretion of T-helper 1 and T-helper 2 cytokines, reduced proliferation to mitogens, and a high in vitro susceptibility to spontaneous (caused by downregulation of bcl-2 expression) as well as activation-induced cell death. A restricted T-cell receptor repertoire was observed, with oligoclonal expansion within each of the dominant segments. These features resemble those observed in γc-/y and in Jak3−/−mice, in which a population of activated, anergic T cells (predominantly CD4+) also develops with age. These results suggest that residual Jak3 expression and function or other Jak3-independent signals may also permit the generation of CD4+ T cells that undergo in vivo clonal expansion in humans; however, these mechanisms do not allow development of CD8+ T cells, nor do they fully restore the functional properties of CD4+ T lymphocytes.

Human equivalent of the mouse Nude/SCID phenotype: long-term evaluation of immunologic reconstitution after bone marrow transplantation

Blood ◽  
2001 ◽  
Vol 97 (4) ◽  
pp. 880-885 ◽  
Author(s):  
Claudio Pignata ◽  
Lucia Gaetaniello ◽  
Anna Maria Masci ◽  
Jorge Frank ◽  
Angela Christiano ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
T Cell ◽  
Marrow Transplantation ◽  
Severe Combined Immunodeficiency ◽  
Combined Immunodeficiency ◽  
Cd8 Cells ◽  
Tcr Repertoire ◽  
Immunologic Reconstitution

Abstract Human Nude/SCID (severe combined immunodeficiency) is the first severe combined immunodeficiency caused by mutation of the winged–helix–nude (WHN) gene, which is expressed in the thymus but not in the hematopoietic lineage. The disease is characterized by a T-cell defect, congenital alopecia, and nail dystrophy. A Nude/SCID patient who underwent bone marrow transplantation from the human leukocyte antigen–identical heterozygote brother was studied to investigate, in this unique model, the role of the thymus in immunologic reconstitution. Despite an increase in CD3+, CD4+, and CD8+cells, CD4+ CD45 RA naive lymphocytes were not regenerated. Conversely, naive CD8+ cells were normal. After an initial recovery, lymphocyte proliferation to mitogens progressively declined compared with controls and genotypically identical donor cells grown in the WHN+/−environment. Analysis of the T-cell receptor (TCR) repertoire of CD4+ cells revealed that only 3 of 18 Vβ families had an altered CDR3 heterogeneity length profile. Conversely, CD8+lymphocytes showed an abnormal distribution in most Vβ families. These data indicate that the thymus is differentially required in the reconstitution of CD4+ and CD8+ naive subsets and in the maintenance of their TCR repertoire complexity. Taken together, these findings suggest that bone marrow transplantation is ineffective in the long-term cure of this form of SCID.

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