R.E. Ballieux

Localization of Human Antigen-Specific Helper and Suppressor Function in Distinct T-Cell Subpopulations

Distinct human T-cell subpopulations were isolated and cultured in the presence of B-cells and antigens. After an incubation period of 6 days cells were tested for their capacity to secrete antigen-specific antibodies in the PFC-assay. The results indicate that the T-helper activity for the antigen-induced T-dependent B-cell differentiation is located in the Tμ-subpopulation, whereas the suppressor-cell activity is confined to the Tγ-subpopulation.

Regulation of B Cell Activity in Man: Role of T Cells

Abbreviations: AC adherent cells cig cytoplasmic immunoglobulin(s) FcyR membrane receptor for the Fc-fragment of IgG ¥cfiR. membrane receptor for the Fc-fragment of IgM He haemocyanine Helix pomatia OA ovalbumin OA-DNP12-11 ovalbumin conjugated with the hapten DNP (ratio 1 to 12-15) PBL peripheral blood lymphocytes PFC plaque-forming cell PNP purine nucleoside phosphorylase PWM pokeweed mitogen SCID severe combined immune deficiency SE sheep erythrocytes TDL tonsil-derived lymphocytes Th T heiper (cell or cells) ThFw T helper factor originating from antigen-stimulated T cells stimulated for 24 h ThFiio T helper factor originating from antigen-stimulated T cells stimulated for 120 h Ts T suppressor (cell or cells) TSB, T suppressor activator cell Tscff T suppressor effector cell TSF24 T suppressor factor originating from antigen-stimulated T cells cultured for 24 h TsFijo T suppressor factor originatingfromantigen-stimuIatedTceUscuUuredforl20h TSpr. T suppressor precursor cell Ty cell T lymphocyte expressing FcyR T^ cell T lymphocyte expressing Fc^R To T lymphocyte without demonstrable Fc/iR and FcyR

Serum immunoglobulins in healthy children and adults levels of the five classes, expressed in international units per millilitre

Serum levels of IgM, IgG, IgA, IgD, and IgE were determined in serum samples of 270 healthy Dutch children (aged 4-13 years) and of 30 healthy Dutch adults, the amounts being expressed in International Units per millilitre. Special attention is given to the IgD and IgE results, since the IgM, IgG, and IgA levels in mg per 100 ml of these sera and their implications have already been reported. In the childrens sera the occurrence of relatively high IgD and IgE levels was frequently observed, whereas the adult group did not show excessive variation in this respect. The mean IgD levels found for adult males and females are 21 I.U./ml and 24 I.U./ml, respectively; the mean IgE levels for the same groups are 68 I.U./ml and 88 I.U./ml, respectively. The mean IgD and IgE levels in the children of each year group were usually higher than those of each of the juvenile groups and the mean level of the adult group was not statistically significant. A statistically significant influence of sex and season on the IgD and IgE levels could not be demonstrated in this material either. Three of the 270 childrens sera showed an exceptionally low IgA content. In two of these cases the serum was sampled and studied a second time after an interval of four years, when the IgA deficiency proved to be still present. The IgE levels in the sera of these healthy IgA-deficient children were normal, whereas the presence of IgD could not be demonstrated.

Acute phase reactants and complement components as indicators of recurrence in human cervical cancer

Twenty patients with invasive cervical cancer of the squamous cell type were treated by radiotherapy and/or radical hysterectomy. During a follow-up period of approximately 2 yr in 10 of these patients a recurrence was established. Serial determinations of three acute phase reactants (α1-acid glycoprotein, haptoglobin and C-reactive protein) and of three complement components (C4, C3-proactivator and C9) were performed before and after therapy and either at the time of recurrence (recurrence group), or at the end of the follow-up period (non-recurrence group). Sequential analysis of the serum levels of all the parameters tested showed a significant increase at the time of recurrence. The most conclusive results were obtained with haptoglobin and the C9-component of complement.

Carcinoembryonic antigen serumlevels in patients with squamous cell carcinoma of the uterine cervix: Clinical significance

In 114 patients with invasive cervical cancer of the squamous cell type pretreatment CEA levels were determined. An individual upper limit of the normal range was derived taking into account the smoking habits and the age of each patient. Pretreatment CEA levels exceeding the upper limit of normal concurred with a very poor prognosis, regardless of the stage of the tumor. Moreover, in 92 patients longitudinal CEA patterns were established. The median follow‐up time of the nonrecurrence patients was four years. Three patterns appeared to be exclusively associated with the presence of recurrent cancer. The median lead‐time obtained in patients demonstrating such patterns, was 13 weeks. The clinical value and the possible therapeutic consequences of the findings presented are discussed in relation to the available knowledge of tumor growth in cervical cancer.

Antigen-induced plaque-forming cell responses in cultures of peripheral blood mononuclear cells of human neonates and infants

Human cord blood mononuclear cells (CBMC) were stimulated in vitro with a number of T cell-dependent antigens. Antigen-induced B cell activation was measured applying a plaque-forming cell assay for the detection of antigen-specific IgM-secreting B cells. With the exception of diphtheria toxoid, the antigens ovalbumin, sheep red blood cells, Helix pomatia hemocyanin, burro red blood cells, and tetanus toxoid elicited an IgM-plaque-forming cell response in cultures of CBMC to levels obtained for peripheral blood mononuclear cells (PBMC) from adult controls. However, for each antigen used, the antigen dose optimal for the induction of a response was consistently found to be a hundred to a thousand times lower than the concentration of the corresponding antigen optimal for adult PBMC. Longitudinal studies on PBMC obtained from infants between 2 and 30 months of age revealed that a shift of the antigen dose toward concentrations needed to induce plaque-forming cells in cultures of adult PBMC occurs at approximately age 8 months. Our data indicate that various antigens can be used for the in vitro analysis of antigen-specific B cell activation and regulatory T cell functions in studies concerning the ontogeny of the humoral immune response in humans.

LYMPHOCYTE SUBPOPULATIONS IN NEONATES, YOUNG CHILDREN AND ADULTS AS DETECTED BY SIX CELL SURFACE MARKERS

Abstract. Gmelig‐Meyling, F., Dollekamp, I., Zegers, B. J. M. and Ballieux, R. E. (University Childrens Hospital “Het Wilhelmina Kinderziekenhuis” and Department of Clinical Immunology, University Hospital, Utrecht, The Netherlands). Lymphocyte subpopulations in neonates, young children and adults as detected by six cell surface markers. Acta Paediatr Scand, 69: 13, 1980.—In this study, six surface marker tests were performed on lymphocytes from normal individuals of three age groups: neonates, children from 0 to 2 years of age, and adults. Determined were the proportions of T cells binding sheep red blood cells, of B cells carrying surface immunoglobulins or binding mouse red blood cells, and of lymphocytes bearing receptors for IgM, for IgG or for complement. The T cell percentage appeared to increase with the age; the percentage of B cells was highest in the childrens group, as determined by both marker tests. Neonates had a much lower proportion of IgM‐receptor bearing cells than older individuals. The variation in the percentages of T cells and of IgM‐receptor bearing cells in the young age groups was relatively large as compared to adults. The significance of these observations is discussed; they may be of value for the proper evaluation of results obtained in diagnostical tests on neonates and young children

Immunoglobulin determination evaluation of the results of immunoelectrophoretic analysis and the radial diffusion method

A comparative study was made of the results of immunoglobulin determination in sera using immunoelectrophoresis and the radial diffusion method of Mancini. The results indicated that, except for certain ranges of immunoglobulin concentration (low, normal or slightly increased) the data obtained by immunoelectrophoresis are unreliable and do not correlate with the values obtained by the Mancini method.

Pathology of immunoglobulins some aspects of monoclonal gammopathy

Human immunoglobulins are a heterogeneous group of proteins closely related in biological function and highly similar in molecular structure. The immunoglobulins are synthesized in cells of the lymphoreticular system. Antigenic stimulation will produce a reaction in the lymphoreticular system in which many different cell clones are involved. This ensures a diffuse increase of immunoglobulins: a

Studies on the antigenic properties of the Fd-fragment of a human G-myeloma protein (Daw)

olyclonal reactionl. Malignant proliferation of a single clone will cause excessive production of a homogeneous immunoglobulin fraction: a monoclonal gammopathyl. One of the aspects of monoclonal gammopathy, viz the presence of an M-component in serum or urine, is the fact that the term “M-component” has begun to lead pretty much its own life as a result of the enormous advances in immunology and profound analytical studies of immunoglobulin structures. Today the term far exceeds its clinical significance. Thus one may find an extensive literature which discusses monoclonal gammopathy as if it were a disease. It is well-advised to bear in mind, however, that one is only dealing with a symptom. The extent to which clinical insights have lagged behind laboratory findings can be illustrated by referring to the fact that, not too long ago, the finding of an M-component was practically tantamount to a diagnosis of multiple myeloma or Waldenstrom’s macroglobulinaemia. But in the years between 1950 and 1960 this simple equation was no longer valid when monoclonal gammopathy was also found to occur in other syndromes2-6.