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Biomedical subjects

R A Good

Publications and source records attributed to R A Good.

At least 433 records · Page 24Linked to original sources
PubMed1981

Restricted antibody formation to sheep erythrocytes of allogeneic bone marrow chimeras histoincompatible at the K end of the H-2 complex.

Employing a new method for allogeneic bone marrow transplantation, irradiation chimeras constructed from various combinations of marrow cells from B10 H-2 recombinant mice and AKR recipients were prepared. Though these chimeras had well-developed populations of T and B cells, they showed strikingly different patterns of responses in the primary antibody formation to sheep erythrocytes (SRBC), a T dependent antigen. These are (a) AKR mice treated with C57BL/10 cells, [B10 leads to AKR] fully H-2 incompatible, and AKR mice treated with B10.A (5R) cells, [5R leads to AKR] I-J,E compatible chimeras that were almost completely unresponsive to SRBC; (b) AKR mice treated with B10.BR cells [BR leads to AKR] fully H-2 compatible, and AKR mice treated with B10 AKM cells, [AKM leads to AKR] chimeras where donor and recipient differed only at H-2D, showed the same number of plaque-forming cells (PFC) as B10 control mice; (c) AKR mice treated with B10.A cells, [B10 leads to AKR] chimeras, where donor and recipient were matched at H-2K-I-E region, showed about one-half the number of PFC as the control mice. From these results we conclude that in allogeneic bone marrow chimeras primary antibody response to T-dependent antigen, such as SRBC, is generated when at least the K end of the H-2 complex is compatible between donor and recipient.

Animals↗
PubMed1981

Evolutionary conservation of surface molecules that distinguish T lymphocyte helper/inducer and cytotoxic/suppressor subpopulations in mouse and man.

We describe the biochemical properties and cell surface distributions of three human T cell antigens (Leu-1, Leu-2a, and Leu-2b) which we postulate to be the homologues of the Lyt-1, Lyt-2, and Lyt-3 antigens that distinguish functional T cell subsets in the mouse. Leu-l, like Lyt-1, is on all thymocytes and peripheral T cells and is present in greater amounts on the helper/inducer subset than on the cytotoxic/suppressor subset. Both antigens increase in parallel fashion during T cell maturation in the thymus and each antigen is carried on a single 67,000-molecular weight (relative) (M(r)) polypeptide chain. Surprisingly, Leu-1 and Lyt-1 each are also expressed in readily detectable amounts on some B celI Ieukemias but not detectably so on normal B cells. Leu-2a and Leu-2b are antigens found only on suppressor/cytotoxic cells in the human and are very similar to the murine Lyt-2 and Lyt-3 antigens. In both species, the two antigens are on the same disulfide- linked multimeric molecules. Disulfide-bond reduction in both species yields subunits of similar size and charge. Lyt-3 and Leu-2b are extremely sensitive to trypsin digestion on viable cells whereas Lyt-2 and Leu-2a are much less so. A different membrane antigen, Leu-3, is an exclusive marker of the helper/inducer subset in man. No mouse homologue for this 55,000-M(r) protein is known. The maintenance of the homologous molecules on functionally distinct T cell subpopulations in two evolutionarily distant species suggests that the Lyt and Leu antigens perform essential functions for the cells on which they are found.

Animals↗
PubMed1981

Evidence that circulating immune complexes remove transfused platelets from the circulation.

Fifteen recently diagnosed patients with acute leukemias admitted for induction chemotherapy were selected for study. When thrombocytopenic (venous platelet count less than 20 X 10(9)/l) these patients received prophylactic platelet transfusions. A total of 67 platelet transfusion therapies were administered and evaluated. Using the Raji cell radioimmunoassay, the serum concentrations of circulating immune complexes (CIC) were measured immediately before and 10-12 hr after each platelet transfusion. In 36 instances, elevated values of CIC were present in the recipient's pretransfusion samples. The corresponding posttransfusion values being significantly lower (P less than 0.05). Furthermore, in those 36 instances the mean percentage for the posttransfusion platelet increment was significantly lower (P less than 0.001) than in the remaining 31 instances in which normal pretransfusion values of CIC were measured. We conclude that CIC were an important factor in rapidly removing transfused platelets from the circulation, thereby, adversely affecting the benefit of platelet transfusions.

Acute Disease↗
PubMed1981

The role of mitogens and antigens in the generation of antibody-producing human B lymphocytes.

Satisfactory experimental systems with which to study the antigen specific humoral immune response of human peripheral blood lymphocytes have not been available until recently. A commonly used method for the study of antibody production by human lymphocytes is that developed by Fauci and Pratt. This system is considered to be antigen nonspecific since the antigen against which the determined antibody is directed is not added to the cultures. We show here that the assumption of the Fauci-Pratt system being antigen nonspecific is not justified. An essential ingredient of this culture system is human serum that has been exhaustively absorbed with antigen (sheep red blood cells). This absorption procedure causes shedding of highly immunogenic antigenic fragments whose immunogenic activity we demonstrated using a recently developed antigen-dependent culture system. In the latter system, we have shown that the control of suppressor cells is a critical factor for the successful induction of antibody responses, particularly in view of the fact that lymphocyte mitogens must be added to cultured human lymphocytes to support their responsiveness. Appropriate timing of mitogen addition to the cultures was found to be an effective means of preferentially stimulating helper or suppressor activity. Pokeweed mitogen, a mitogen known to act on B and on T lymphocytes, Stimulates B cells responses readily but abrogates them prematurely by the simultaneous activation of suppressor cells. When pokeweed mitogen is added to an ongoing response with a delay of 48 hr, it enhances antibody responses markedly, presumably by providing additional help to B cells at a time when they have lost susceptibility to suppressor-cell effects.

Absorption↗
PubMed1981

Defective cellular immune response in vitro in common variable immunodeficiency.

Mononuclear cells from 39 patients with hypogammaglobulinemia of the common variable type were analyzed for in vitro proliferative response to a panel of cell activators in order to examine the lymphocyte response to mitogens and to study the capacity to generate an immunologically specific secondary response. Patient lymphocyte response to phytohemagglutinin and concanavalin A was found to be significantly lower than that of controls studied in parallel (P less than 0.01), and low response did not correlate with T-lymphocyte number. Response to pokeweed mitogen was significantly lower than that of controls (P less than 0.01), but response to zinc, tested in a few patients, was normal. Strong depressions of patient lymphocyte proliferative responses to Candida albicans, Escherichia coli, and Staphylococcus aureus were observed (P less than 0.01); all of these microbial activators require intact B-cell function for maximum response. Repeated testing of individual patients indicated that poor lymphocyte response could be consistently observed. Examination of change in vitro lymphocyte response during clinical course and disease management showed that a consistent pattern of intrinsic lymphocyte functional deficiency could be demonstrated.

Adolescent↗
PubMed1981

Marrow transplantation for juvenile osteopetrosis.

Two children with the juvenile form of osteopetrosis were treated with marrow transplants from their HLA identical siblings. Following transplantation each child exhibited extensive bone reabsorption with a marked augmentation of osteoclastic function attributable to donor osteoclasts, including remodeling of bone with expansion of intramedullary hematopoiesis and correction of associated abnormalities of thymic factor and natural killer cells. Osteopetrosis ultimately recurred in one patient in whom engraftment of donor hematopoietic elements was not achieved. Our studies indicate that marrow transplantation will correct osteopetrosis but that permanent reconstitution necessitates sustained engraftment of marrow precursors of cells with osteoclastic activity.

Bone Marrow Transplantation↗
PubMed1981

The role of an adherent cell in the production of monocyte chemotactic factor.

The functional role of an adherent cell in assisting a variety of in vitro immune responses is well established. An assay for human monocyte chemotaxis in vitro was utilized as a means of investigating the role of adherent cells in the production of the monocyte chemotactic factor that is produced by peripheral blood lymphocytes upon stimulation with Concanavalin A. Depletion of a population of adherent cells by passage of peripheral blood mononuclear cells through a Sephadex G-10 column rendered the latter incapable of producing monocyte chemotactic factor. The requirement for adherent cells in the production of a "lymphokine" is in agreement with many previous works of a similar nature performed in other experimental systems.

Cell Adhesion↗
PubMed1981

Thymus-dependent membrane antigens in man: inhibition of cell-mediated lympholysis by monoclonal antibodies to TH2 antigen.

In prior studies a heteroantiserum to a surface membrane component termed T(H2) was used to define two subsets of human T cells (T(H2) (+) and T(H2) (-)), which were found to express distinct sets of activities in vitro. In the present studies we prepared monoclonal antibodies to surface determinants that are restricted to T cells belonging to each of these two subsets. Two antibodies, termed alphaLeu-2a and alphaLeu-2b, which seem to define the same surface antigen identified by the original T(H2) antiserum, reacted with 57-84% of thymocytes and 22-46% of the erythrocyte-rosette-forming cells (ERF-C) in peripheral blood. Two other monoclonal antibodies, termed alphaLeu-3a and alphaLeu-3b, reacted with the same subpopulation of thymocytes (78-89%) and peripheral blood ERF-C (47-78%) but, unlike alphaLeu-2a and alphaLeu-2b, did not exhibit cross-blocking; i.e., labeling cells with alphaLeu-3a did not inhibit the subsequent binding of alphaLeu-3b. T cells reactive with alphaLeu-2a were shown to be unreactive with alphaLeu-3a, indicating that two separate subpopulations of T cells, Leu-2 (formerly T(H2) (+)) and Leu-3 (T(H2) (-)) T cells, were thereby defined. These two T cell subsets make up the subpopulation of ERF-C (80-95%) previously defined by a monoclonal antibody to a T cell membrane antigen (Leu-1) that has a thymus-dependent distribution on normal lymphocytes but is expressed by some surface-immunoglobulin-positive (sIg(+)) leukemic lymphocytes. None of the Leu antibodies reported here reacted with sIg(+), Leu-1(+) leukemic cells, nor did they react with normal hematopoietic cells or lymphoid cells that had surface markers characteristic of B cells. Studies of the blocking effects of Leu antibodies on killing in cell-mediated lympholysis by effector T cells were carried out in the absence of complement. These experiments established the following points: (i) alphaLeu-2a abolished the killing by cytotoxic T cells of allogeneic phytohemagglutinin-stimulated blasts, (ii) inhibition of killing by alphaLeu-2b was markedly less than inhibition by alphaLeu-2a, and (iii) other antibodies, including alphaLeu-1, alphaLeu-3a, and alphaLeu-3b, had little or no effect on killing in cell-mediated lympholysis. The relevance of these findings to prior studies done in the mouse and in man are discussed.

Animals↗