Jacqueline Breard

Characterization of the human blood lymphocytes that produce a histamine-induced suppressor factor (HSF)

Abstract The cells which elaborate a soluble suppressor factor in vitro in response to histamine (histamine-induced suppressor factor or HSF) were partially characterized in the present studies. Human blood T- and B-cell populations were purified by affinity chromatography with rabbit anti-human F(Ab′)2 and examined for their ability to make HSF. Highly purified populations of T cells, but not B cells, produced HSF in response to varying concentrations of histamine (10−4 to 10−4M). The HSF-producing cells were characterized further by means of affinity chromatography with columns containing conjugates of insolubilized histamine as well as by rosette formation with IgG (Tγ)- or IgM (Tμ)-coated ox red blood cells. These studies revealed the following: (a) Cells that synthesize HSF are retained on histamine (but not control) columns; (b) cells with histamine receptors comprise approximately 50% of the Tγ subpopulation but are not found in the Tμ subpopulation; (c) cells not retained by histamine columns have a reduced capacity to develop into suppressor cells following stimulation by concanavalin A or specific antigen (compared to unfractionated or control column passed cells). In addition, it was shown that cells synthesizing HSF predominantly express histamine type 2 receptors: (d)4-Methyl histamine (H2 agonist), but not 2-methyl histamine (H1 agonist), was capable of inducing HSF production; (e) cimetidine (H2 antagonist) inhibited HSF production but chlorpheniramine (H1 antagonist) did not. Taken together, these experiments suggest that T lymphocytes capable of expressing suppressor function following activation by histamine, specific antigen, concanavalin A, or perhaps through their Fc receptors may either be heterogeneous within the same subpopulation or more likely be the same cell with the complement of receptors described above.

Delineation of an effector population responsible for natural killing and antibody-dependent cellular cytotoxicity in man

Abstract A series of three monoclonal antibodies to human lymphoid cell surface determinants was utilized to characterize the effector population for natural killing (NK) and antibody-dependent cellular cytotoxicity (ADCC). The first antibody, termed anti-T3, was reactive with all peripheral T cells (T3 + ); a second defined an invariant region of the human Ia antigen found on all B cells and a fraction of monocytes and Null cells (Ia + ); and a third, anti-M1, reacted with circulating monocytes (MI + ). Complement-mediated lysis was employed to eliminate M1 + , T3 + , and/or Ia + cells. It was found that removal of the M1 + population markedly reduced ADCC as well as NK. In contrast, lysis of T3 + and Ia + cells enriched for both functions. These observations suggest that the major effectors of NK and ADCC among resting peripheral blood mononuclear cells are restricted to the M1 + , Ia − population.

Lymphoid subpopulations of peripheral blood and spleen in untreated Hodgkin's disease.

A panel of monoclonal antibodies with well‐defined specificities were used as probes to investigate the phenotypes and lineage of circulating lymphoid cells and splenocytes in untreated patients with Hodgkins disease. A signficant relative and absolute reduction in T cells (anti‐T3+) was found only in patients with B‐symptoms. There was no alteration in the fraction of helper (anti‐T4+) or cytotoxic/suppressor (anti‐T5+) T cells circulating in peripheral blood when compared to normals, nor was there activation of these cells as measured by the development of surface Ia (anti‐I1+). Circulating T cell subsets were not altered 5 to 14 days after splenectomy. Splenic T cells were increased equally in involved and uninvolved spleen when compared with control spleens obtained from accident victims. These findings indicate that abnormal T cell function in Hodgkins disease may be the result of subtle alterations in T cells or non‐T immunoregulatory mechanisms.

Normal erythropoietic helper T cells in congenital hypoplastic (Diamond-Blackfan) anemia.

To examine the erythropoietic function of T and null cells in congenital hypoplastic (Diamond-Blackfan) anemia, we fractionated the peripheral blood of three normal subjects and three affected patients into subclasses of null, T and B cells. Mixtures of these cells were co-cultured in plasma clots in the presence of erythropoietin. Erythroid colonies grew in cultures of normal null cells if either normal or patient T cells were co-cultured with them. Null cells of patients with hypoplastic anemia did not produce erythroid colonies under any culture conditions. We conclude that in this disorder, T cells function normally as helper cells in erythropoiesis and do not suppress colony formation, whereas the erythroid progenitor cells in the peripheral blood null-cell fractions are deficient in either number of function.

The role of p23,30-bearing human macrophages in antigen-induced T lymphocyte responses☆

Abstract The effect of anti-p23,30, a rabbit antiserum to the human Ia-like antigen p23,30, on two macrophage-dependent T-cell functions, proliferation in response to soluble antigens, and production of lymphocyte mitogenic factor (LMF) was studied. T cells depleted of macrophages neither proliferate nor secrete LMF, and these functions are restored by addition of as few as 0.5% adherent macrophages. Treatment of macrophages with anti-p23,30 and C, however, abolishes their capacity to reconstitute these T-cell functions. In contrast, treatment of T cells with anti-p23,30 and C did not affect their capacity to respond in the presence of untreated adherent cells. We conclude that the presence of p23,30-bearing macrophages is critical for the expression of these antigen-induced T-cell responses.