Alloantibodies reacting exclusively with PHA-activated T lymphocytes.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to D M Silver.
Explore the source record for details and available documents.
Two hundred and three sera obtained from multiparous women were screened to determine the frequency of the appearance of antibodies reactive with PHA-activated T lymphocytes, but not with resting B or T cells from the same donor. The panel of cells on which the sera were tested consisted of lymphocytes from 38 unrelated donors known to be homozygous at the HLA-D locus. Forty-two sera were shown to react uniquely with PHA-activated T cells. The reactivities of these sera could not be explained in terms of the defined HLA-A,-B,-C, or DR antigen specificities on the panel cells, nor on the basis of known cross-reactivities among these antigens. Most of the antisera showed strong cytotoxicity with the activated T cells. Such sera may define antigens presented to the maternal immune system during differentiation and development, which are not expressed on adult T cells unless they are activated.
A 2 1/2-year-old male infant with severe combined immunodeficiency was documented by HLA typing and the presence of a female karyotype in the few spontaneously dividing cells to have an intrauterine-derived maternal lymphocyte graft. The presence of DR antigens on the engrafted maternal E rosette-forming T cells was demonstrated by both cytotoxicity and immunofluorescence techniques using both conventional and monoclonal antihuman DR antisera. These DR antigens were of the same allospecificity, DR4, as the mother's peripheral blood B cells. The patient's B cells and monocytes expressed DR alloantigens DR4 and DR3, corresponding to his genotype. Although fresh maternal lymphocytes react strongly in vitro against patient non-T cells, the engrafted maternal T lymphocytes no longer show this activity. Furthermore, clinical evidence suggesting mild graft-versus-host disease was completely resolved by the end of his first year. The presence of the DR-positive maternal cells may reflect the survival of a group of activated suppressor cells mediating graft tolerance of host tissue.
Explore the source record for details and available documents.
In response to multiple injections of liver extract from Balb/c mice, DBA/1 mice produce antibodies against a component of the liver preparation which is not F-antigen, but which is able to precipitate in gel diffusion tests. This antigen is also found in extracts of Balb/c lung, but not in a variety of other organs tested. Liver extracts from all of the inbred strains studied contain the antigen, except extracts from DBA/1 mice. Furthermore, this antigen was not found in the liver or lungs of other vertebrates tested. The antigen has been designated antigen-L1.
Explore the source record for details and available documents.
The autoantibody response induced in mice by alloimmunization with liver-specific F antigen is an example of the circumvention of humoral self-tolerance. The F molecule has been isolated and shown to be a protein with a mol. wt. of 40 000 Daltons which migrated as a beta-globulin. The purified antigen retains both the immunogenic and antibody-combining properties of crude liver homogenate. Successful iodination of the protein allowed the establishment of a radioimmunoassay which demonstrated high titers of antibodies in responder strains. At the same time it was clearly shown that no antibody could be detected, either as a result of syngeneic immunization or as a result of alloimmunization in nonresponder strains. The characteristics of the F antigen immune response distinguish it from that induced by other proteins.
The liver-specific F antigen, although not an autoimmunogen, can induce the production of autoantibodies in responder strains. The ability to respond is under the control of two genes, one linked to the H-2 locus of mice, the other not. Responders possessing both genes produce high anti-F titers, while the H-2-linked gene alone permits a significant but low antibody response. (Responder X nonresponder) F1 hybrids derived from parents possessing identical F molecules are nonresponders, in contrast with the dominance of responsiveness in Ir gene systems. The presence of the H-2 locus from nonresponders appears involved in the inability to respond. This is discussed in terms of self-tolerance and suppression.
The immune response to sheep red blood cells (SRBC) has been studied in two mouse lines selectively bred for a difference in leukocyte levels. Low leukocyte count (LLC) mice responded to multiple injections of 4 x 10(7) SRBC with a predominant IgM response whereas high leukocyte count (HLC) mice produced IgG almost exclusively, even after a single injection of SRBC. F1 mice responded like the LLC parent and backcross data implied genetic control at multiple loci. No correlation was found between the class of antibody produced in response to SRBC and the leukocyte count in backcross mice. Large numbers of plaque-forming cells (PFC) were detected in the spleens of HLC mice relative to the number detected in LLC spleens after primary and secondary immunizations with SRBC.
Explore the source record for details and available documents.
In response to repeated injections of sheep red blood cells, C57BL/10J mice produce predominantly 19S antibody in increasingly higher amounts, while A/J mice initially produce 19S antibody and then switch to produce increasing 7S antibody titers. In an F(1) generation all mice responded like the C57BL/10J mice. Backcross data implied genetic control involving at least three loci.
Explore the source record for details and available documents.
Explore the source record for details and available documents.