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Biomedical subjects

C B Carpenter

Publications and source records attributed to C B Carpenter.

At least 145 records · Page 8Linked to original sources

Transfer of specific unresponsiveness to organ allografts by thymocytes. Specific unresponsiveness by thymocyte transfer.

Prolonged survival of vascularized organ allografts has been produced in unmodified inbred rats by transfer of thymocytes from enhanced, engrafted, syngeneic animals. For these thymocytes to increase significantly the survival of test allografts they must be harvested 6-9 d after transplantation. Thymectomy of the enhanced, engrafted animals during the same critical period causes acute rejection of othewise long surviving grafts. For optimal effect, the enhanced thymocyte donor must be actively and passively immunized and receive a cardiac allograft. The necessity for erythrocytes in the initial active immunization regimen is noted. Additionally, the antigenic specificity of the suppressor effect has been established with two histoincompatible donor rat strains. Cellular and humoral host responses mounted by test graft recipients after thymocyte transfer from enhanced, engrafted donors are different from those mounted either by unmodifed animals acutely rejecting their grafts or by enhanced rats bearing well-functioning grafts. Numbers of T lymphocytes are reduced in the grafted hearts and in the spleens of test graft recipients, a finding paralleled by the complete absence of specific direct lymphocyte-mediated cytotoxicity. In contrast, cytotoxic antibody production, although delayed, is increased in magnitude, peaking around the time of graft rejection. These studies provide evidence that different biological manipulations can modify separate pathways in the complex cellular and humoral responses towards organ allografts. They demonstrate that cellular immunity is critically involved in immunological enhancement of vascularized organ allografts, a phenomenon hitherto considered primarily humoral. It seems clear that cells with suppressor activity are present within the thymus during the early phases of immunological enhancement.

Animals↗

Mechanisms in the suppression of delayed hypersensitivity in the guinea pig by 6-mercaptopurine. II: Kinetic and morphologic studies on the monocyte-macrophage component.

The effect of 6-mercaptopurine on the development and expression of delayed hypersensitivity was studied in the guinea pig. Results indicated that 6-MP produced its suppressive effects primarily by action on cells of the monocyte-macrophage series. Suppression could occur under conditions of both developing and pre-established delayed hypersensitivity. The defect primarily involved newly synthesized, bone marrow-derived monocytes. Marked alterations in monocyte macrophage generation and distribution, especially the T1/2 of circulating monocytes were demonstrated. Suppressive effects were associated with the appearance of a unique morphologic microscopy. Finally, the in vivo expression of delayed hypersensitivity correlated better with a variety of parameters relating to qualitative macrophage function and distribution rather than those relating to quantitative macrophage levels.

Animals↗

Rejected human renal allografts: recovery and characteristics of infiltrating cells and antibody.

Viable infiltrating host leukocytes have been isolated from 10 rejected human renal allografts, removed 1 to 67 months after transplantation. The cell populations have been identified by surface characteristics and their cytotoxic capacities were assessed. A heterogenous population of cells of host origin accumulated in the grafts, including T and B lymphocytes, Fc+ cells, and macrophages. Using a 51Cr release assay, specific cytotoxicity against donor alloantigens was determined. Cytotoxicity of the infiltrating cells was almost invariably greater than cytotoxicity mounted by recipient peripheral blood lymphocytes. Deletion studies confirmed previous work and suggested that T cells were primarily responsible for cytolysis in early acute rejection; non-T cells more often in late chronic rejection. Antibodies eluted from the grafts demonstrated both specific antidonor and nonspecific activity as well as cross-reacting anti-HLA activity. Allograft morphology was examined and cellular and humoral host responses were assessed. These studies emphasize the complexities of immune responses produced by the host against transplanted tissues.

Antibody Specificity↗

Improved B cell typing for HLA-DR using nylon wool column enriched B lymphocyte preparations.

A rapid, simple procedure for preparing B lymphocytes using nylon wool has been devised. When mixtures of T lymphocytes, B lymphocytes, and monocytes are applied to nylon wool columns, B lymphocytes can then be removed, virtually free of monocytes. Such preparations (Ad) are 85 +/- 6% SIg+ and have only 3 +/- 1% monocyte contamination. The yield from peripheral blood averages 5% of all mononuclear cells. In contrast, the E rosette depletion method (E-) yields cells which are only 64 +/- 5% SIg+ and have 25 +/- 7% monocyte contamination. The superiority of the nylon method for HLA-DR typing was demonstrated in a comparative study of Ad and E- with eight normal individuals. Cytotoxic scores were higher and a large number of reactions, representing DRw groups and additional cross-reactions, was detected.

B-Lymphocytes↗

Mapping of the structural gene for the second component of complement with respect to the human major histocompatibility complex.

Families have been HLA typed, and allotypes of the second component of complement and properdin factor B determined. The lod score for the C2 structural gene and HLA-B from the study of 11 families and 55 informative meioses was 14.39 at maximum likelihood estimate of the recombination fraction of .02. This is related to other estimates of the distance between these two genes. The relative kinetic activities of the C2 allotypes were studied and no differences were demonstrated. No crossovers between Bf and C2 were observed.

Adult↗