Heterogeneity of lymphocyte subpopulations in severe combined immunodeficiency. Evidence against a stem cell defect.

Abstract

A B S T R A C T Surface markers typical of T and B lymphocytes were present on varying proportions of peripheral blood lymphocytes from three infants with severe combined immunodeficiency disease. Despite this, functions mediated by T and B cells were either absent or very minimal in all three, including cell-mediated responses in vivo; the in vitro proliferative response to mitogens, allogeneic cells, or antigens; effector cell function in lymphocyte-antibody lymphocytolytic interaction assays; and in vitro synthesis of IgG, IgA, and IgM. In contrast, mononuclear cells from one of the infants were tested and found capable of lysing both human and chicken antibody-coated erythrocyte targets normally. Co-cultivation experiments with unrelated normal control lymphocytes failed to demonstrate suppressor cell activity for immunoglobulin synthesis in these infants. Augmentations of immunoglobulin production from 310 to 560% over that expected on the basis of individual culture data were noted in co-cultures of one of the infants' cells with two different unrelated normal control cells. These findings suggest that that infant may have had a T helper cell defect or that his T cells were unable to produce soluble factors necessary for B cell differentiation. The finding of cells with differentiation markers characteristic of T and B lymphocytes in each of these patients, though in variable quantities, is further evidence for heterogeneity among patients with the clinical syndrome of severe combined immunodeficiency and Dr.

Use of a human plaque-forming cell assay to study peripheral blood bursa-equivalent cell activation and excessive suppressor cell activity in humoral immunodeficiency.

“…Key among these is the recent appreciation that such disorders may not all be caused by an intrinsic inability of stem cells to fully differentiate into mature lymphoid cells (1)(2)(3)(4). In some forms of immunoglobulin deficiency, apparently mature bursa-equivalent (B) lymphocytes are present in normal numbers (2).…”

Immunoregulation in an Isolated 12-year-old Boy with Congenital Severe Combined Immunodeficiency

“…The basis for this paradox is believed to be the abnormal differentiation of B and T cell precursors (22). Inadequate numbers of helper T cells have been implicated in a few patients (4,24) and several authors have also suggested a role for excessive numbers of suppressor T cells, which has been documented in at least one case (21). Certainly other forms of immunodeficiency, including subgroups of patients with common variable hypogammaglobulinemia selective IgA deficiency, and X-linked agammaglobulinemia; have been described with increased numbers or function of suppressor T lymphocytes (1,25,27).…”

Heterogeneity of b lymphocyte differentiation in severe combined immunodeficiency disease.

“…1). Suppression was occasionally noted in cocultures containing cells from patients (19) in anotherassay system. However, the likelihood that suppressor cells can play a role in the immunodeficiency of SCID be- (26,27) and Gelfand et al (4,28), and such patients might be immunologically reconstituted by treatment with thymus transplantation alone.…”

“…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.…”