Selective defect of precursor T cells associated with apparently normal B lymphocytes in severe combined immunodeficiency disease

Evaluation of HLA-Haplotype Disparate Parental Marrow Grafts Depleted of T Lymphocytes by Differential Agglutination with a Soybean Lectin and E-Rosette Depletion for the Treatment of Severe Combined Immunodeficiency

“…Previous studies of patients who developed only host B lymphocytes following HLA-identical marrow grafts [46,47] have suggested that the B lymphocytes detected in most (but not all) [48] patients with SCID are intrinsically normal, and can generate antibodies to specific antigens if induced to do so by the engrafted T helper cells of the have detected in up to 40% of patients with SCID, did not correlate with engraftment or graft resistance.…”

“…Following the initial successful application of HLAcompatible bone marrow transplantation for the treat ment of severe combined immunodeficiency (SCID) [1] and Wiskott-Aldrich syndrome [2] in 1968, transplants of HLA-identical marrow rapidly emerged as a potentially curative treatment of choice for several lethal, congenital disorders of the immune system, including the following: various forms of SCID [3][4][5], Nezelof s syndrome [6][7][8], bare lymphocyte syndrome [9], reticular dysgenesis [10], cartilage-hair hypoplasia syndrome [11,12], WiskottAldrich syndrome [13][14][15], and the Chédiak-Higashi syn drome [16]. Results of transplants for these and other congenital disorders have recently been reviewed [17], Unfortunately, normal HLA-identical sibling donors are available for only about 40% of cases.…”

Heterogeneity of b lymphocyte differentiation in severe combined immunodeficiency disease.

“…Mononuclear cells were first isolated by floatation on metrizoate/Ficoll cushions and then further fractionated by velocity sedimentation at unit gravity (7). Cells from different fractions were pooled to yield the following cell populations: pool 1 (fractions [1][2][3][4][5][6][7][8][9][10], consisting largely ofcells ofthe myeloid series; pool 2a (fractions 11-13), consisting mainly of monocytes and a few large lymphocytes; pool 2b (fractions 14-16), containing predominantly medium sized lymphocytes; and pool 3 (fractions [17][18][19][20][21][22][23][24], containing mainly small lymphocytes.…”

“…Proportions ofT lymphocytes in peripheral blood are markedly reduced, but numbers of B lymphocytes are very heterogenous, ranging from complete absence to increased proportions, and even increased absolute numbers. Although B and T lymphocyte function in these patients is grossly deficient in vivo, B cells from some patients have been shown to undergo terminal differentiation in vitro in the presence ofpokeweed mitogen (PWM) and normal T cells (2,3). Antigen-specific antibody producing plaque-forming cells have been shown to be generated in peripheral blood mononuclear cells of one patient with SCID after their incubation with thymic epithelial monolayers (4).…”

Immunoreconstitution by Peripheral Blood Leukocytes in Adenosine Deaminase-deficient Severe Combined Immunodeficiency

“…Although severe combined immunodeficiency can result from a number of pathogenetic mechanisms (1)(2)(3)(4), the treatment of choice is transplantation of normal lymphoid precursor cells to establish a new clone of self-replicating cells that differentiate into functional lymphocytes. The two tissues that have been used as a source of lymphoid precursor cells are bone marrow and fetal liver.…”