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Biomedical subjects

W Boyle

Publications and source records attributed to W Boyle.

At least 55 records · Page 3Linked to original sources

The antigen-specific signal in T-lymphocyte activation by alloantigen.

Current concepts of the mechanism of alloactivation of cytotoxic lymphocytes and the identity of the target cell determinants with which they interact are reviewed. The results of a quantitative analysis of the stimulatory activity of different forms of antigen and the role of a costimulator factor are presented. These lead to the conclusions that SD antigens are not the target cell antigens and that existing theories of cytotoxic T cell activation are inadequate. A new theory of activation of alloareactive cytotoxic lymphocytes is proposed.

Animals↗

A micro-version of the 51Cr release assay for cytotoxic lymphocytes.

A micro-version of the 51Cr release assay for cytotoxic lymphocytes has been devised, which is conducted in Terasaki plates, in a total reaction volume of 8 microliter. The conditions necessary to make the microassay equivalent in sensitivity and reproducibility to the standard macroassay are described. In comparison with the standard macroassay, the microassay provides a 10-fold reduction in the number of effector cells employed and represents a 50-fold reduction in reaction volume. The assay has been particularly valuable in the saving of antisera when these are employed to block target cell lysis, or to selectively inactivate cells of a particular phenotype in the effector cell population.

Animals↗

Daily monitoring of the immune response to various allografts in rats.

The appearance of activated lymphocytes and antibodies in the circulation of rats was monitored following allogeneic kidney, skin, or combined skin-spleen transplants. Lymphocyte activation was measured by 3H-thymidine incorporation, and antibody by a hemolytic assay. These assays have been developed so that small samples of blood could be used, thus maintaining recipient survival and allowing for daily correlation between the response observed and the fate of the graft. These responses were detected after allogeneic transplantation in two recipient strains, but not following isogeneic renal or skin transplantation in either strain. The relative levels, time of onset and persistence of lymphocyte proliferation and of hemolytic antibody were found to differ substantially for the three different kinds of allografts. In general, these studies have demonstrated the validity of using the lymphocyte proliferative and humoral responses together as indicators of a current immune response against allogeneic renal transplants.

Animals↗

Induction of cytotoxic lymphocytes directed against public alloantigens.

The response of H-2k lymphocytes to in vitro stimulation by H-2b and HI2d spleen cells has been monitored for the production of cytotoxic lymphocytes (CL). Using cells from H-2b strains CL which were capable of lysing both H-2b and H-2d target cells (TC) were generated. These results, together with competitive inhibitor studies of the cytotoxic activity against H-2d TC, demonstrated that T lymphocytes can respond to both public and private alloantigens of the H-2 complex. When H-2d cells were used for stimulation two of the three strains tested induced CL with cytotoxic activity towards both H-2d and H-2b TC. These observations indicate that the T cell response to alloantigen, leading to the production of cytotoxic lymphocytes, can be multicomponent like the established B cell response and can be expected to be subject to as much phenotypic variation. The full complexity may only be revealed by examing a number of combinations of stimulating strains, methods of stimulation and different kinds of target cells.

Animals↗

Cell-mediated immune response in vitro. 3. The requirement for macrophages in cytotoxic reactions against cell-bound and subcellular alloantigens.

All efficient cell separation procedure and specific anti-macrophage serum were used to investigate the requirement of macrophages in the in vitro allograft response of mouse lymphoid cells. The efficiency of the macrophage-depletion procedure used and the undiminished capacity of the purified lymphocytes to respond were verified by also testing the antibody responses to sheep red cells (SRC) and dinitrophenylated polymeric flagellin (DNP POL) as well as the proliferative response to allogeneic cells. It was found that the generation of cytotoxic lymphocytes were diminished after macrophage depletion by surface adherence. The combination of anti-macrophage serum and column purification resulted in the total abolition of cytotoxic activity. The cell-mediated immune response was restored completely by addition of peritoneal macrophages, with as few as 1 macrophage to 600 lymphocytes permitting a significant restoration. Macrophages were not involved in the cytotoxic effector phase, but were essential in immune induction. A subcellular H-2 alloantigen preparation was only immunogenic in the presence of macrophages, indicating that a mere reduction in the size of the antigen from cell-bound alloantigens to membrane fragments was not the sole function of macrophages. The results suggest that macrophages collaborate with T cells in the initiation of an allograft response in vitro.

Animals↗