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Biomedical subjects

D A Rowley

Publications and source records attributed to D A Rowley.

At least 73 records · Page 4Linked to original sources
PubMed1977

Immune response to phosphorylcholine. III. Requirement of the Fc portion and equal effectiveness of IgG subclasses in anti-receptor antibody-induced suppression.

Anti-idiotypic antibody raised against the BALB/c myeloma proteins TEPC-15 or HOPC-8 inhibits induction of the immune response to phosphorylcholine (PC). (Fab')2 and Fab' fragments from anti-idiotype serum were prepared and anti-idiotypic antibody was purified by absorption and elution from idiotype or anti-IgG subclass immunoabsorbents. The parent material, the purified anti-idiotypic antibodies and the Fab' fragments were assayed for: i) binding to the idiotype by using a sensitive radioimmunoassay, and ii) specific suppression of the response to PC in vitro. The correlation of binding to suppression was very similar for anti-idiotype serum and both kinds of purified antibody. However, the Fab' fragments only bound to the idiotype and did not suppress. These findings indicate that the Fc portion of anti-idiotypic anti-receptor antibody (ARA) is essential for inducing suppression but that ARA-induced suppression is independent of the IgG isotype. It is postulated that idiotype suppression is mediated by the interaction of anti-idiotype with the antigen receptor and the Fc receptor thereby cross-linking both receptors.

Animals↗
PubMed1976

Suppression by autogenous complementary idiotypes: the priority of the first response.

Complementary idiotypes or antibodies are considered to have combining site structures which are at least partly directed against each other. Complementary antibodies were induced in A/He mice by immunization with phosphorylcholine (PC)-containing antigens and by immunization with the PC-binding IgA myeloma protein TEPC-15 (T15). Both responses were monitored by enumerating plaque-forming cells (PFC) and assaying serum antibody levels against the corresponding antigens. Mice immunized at least three times with T15 in adjuvants had markedly suppressed responses to subsequent immunization with PC; similarly, mice preimmunized multiple times with PC had suppressed responses to immunizations with T15. In contrast, mice immunized with T15 in the interval between "primary" and "secondary" immunizations with PC had undiminished PFC responses to both antigens but significantly decreased antibody titers to PC. Simultaneous responses were also induced by immunizations with T15 superimposed on weekly immunizations with PC; with this regime, immunization with T15 actually enhanced the PFC response to PC, but serum antibody to PC was significantly lower than for mice immunized with PC only. Levels of serum antibody to PC were probably lower, either because anti-PC antibody was complexed with the complementary antibody directed against T15, or because the antibody directed against T15 prevented synthesis and/or release of anti-PC antibody by cells in vivo. Thus, an established prior autogenous immune response can dramatically suppress a subsequent primary complementary response, but the effects of complementary responses on each other are more complex with different sequences of immunization. Also, the effects of variables such as the amounts and ratios of the classes of antibodies on regulation of complementary responses remain to be defined.

Animals↗
PubMed1976

Antibody against the antigen receptor of a plasmacytoma prolongs survival of mice bearing the tumor.

A transplantable plasmacytoma, TEPC-15 in BALB/c mice, induces a transient antibody response directed against the combining region of the myeloma protein produced by the tumor. Mice immunized with mitomycin-treated tumor cells produce similar antibody but do not develop tumor; mice so immunized survive longer than untreated mice when inoculated with viable TEPC-15 cells. This protection afforded by immunization can be transferred by serum alone; the protective effect of passively given serum is eliminated by absorbing out antibody directed against the myeloma protein.

Agglutinins↗
PubMed1975

Specific suppression of the antibody response in vitro by serum from paralyzed mice.

BALB/c mice immunized with either the whole vaccine or the C-polysaccharide obtained from the R36A strain of pneumococcus produce antibody to phosphorylcholine. Mice injected i.v. with a single high dose of the C-polysaccharide are specifically unresponsive to immunization to phosphorylcholine for many months and are considered paralyzed. The induction of paralysis does not eliminate cells reactive to phosphorylcholine; however, serum from paralyzed mice specifically suppresses the response of cultures of normal spleen cells to phosphorylcholine. Paralyzed mice have an early low antibody response to phosphorylcholine and to the receptor for phosphorylcholine as indicated by plaque-forming cell assays. The factor or factors present in serum which may suppress cultures, and, by presumption, be responsible for paralysis are complexes of antigen, antibody, and antibody to the receptor for phosphorylcholine.

Animals↗
PubMed1975

Anti-receptor antibody. II. Induction of long-term unresponsiveness in neonatal mice.

We have examined the ability of anti-receptor antibody (ARA) to induce specific unresponsiveness to the hapten, phosphorylcholine (PC), in neonatal and adult mice. When ARA is given to adult mice, suppression is of short duration. Cells from such mice are responsive in vitro, indicating that suppression in vivo is probably due to blockade of receptors by persisting ARA. ARA given to neonatal mice induces long-term unresponsiveness. The mice apparently have decreased numbers of PC-responsive cells, since cells from such mice are unresponsive both in vitro and in adoptive transfer. Furthermore, cells from neonatally suppressed animals do not suppress the response of normal cells either in vitro or in adoptive transfer, indicating that unresponsiveness is most likely not due to active suppression. We therefore conclude that ARA given to neonates depletes the clone of receptor-bearing cells at the time ARA is given. Clonal depletion may result from antibody-dependent cell mediated cytotoxicity.

Animals↗
PubMed1974

Neonatal tolerance induced by antibody against antigen-specific receptor.

Specific immunologic unresponsiveness is induced by injecting adult or neonatal mice with antibody against antigen-specific receptor (antireceptor antibody). Suppression in mice treated as adults lasts several weeks, and cells from these suppressed mice respond normally in culture. In contrast, unresponsiveness induced in neonatal mice is long-lasting; cells from these mice do not respond in culture and do not affect the response of normal cells. Evidently, antireceptor antibody reversibly blocks antigen receptors in adult animals, but induces unresponsiveness in neonatal mice by depleting the clone of receptor-bearing cells.

Animals↗
PubMed1973

Specific suppression of immune responses.

The models we have discussed in detail demonstrate specific suppression of immune reactivity produced in normal adult animals by antibody and antigen. The mechanism of homeostasis of suppression in these models depends on continued exposure to antigen and on an active response by the host. The active response may include production of antibody directed against specific receptors as well as antibody directed against antigen. Thus, specific regulation of both antibody and cell mediated immunity to an antigen might be achieved by the use of only the biological agents of the response: antigen, antibody, and possibly antibody to receptors. The general implication is that these same biological agents are responsible for autoregulation of immune reactions occurring in nature. Presumably, these agents may be used to suppress or reverse immune responses for appropriate clinical objectives.

Animals↗
PubMed1972

The specific selection of recirculating lymphocytes by antigen in normal and preimmunized rats.

Thoracic duct lymphocytes (TDL) from normal rats will restore a primary antibody response to sheep erythrocytes (SRBC) in irradiated recipients and cause a graft-versus-host reaction in F(1) hybrid rats; lymphocytes from rats immunized with either tetanus toxoid or dinitrophenylated bovine gamma globulin (DNP BGG) will generate specific antibody after cell transfer and challenge. The ability of TDL to mediate each of these responses is severely depressed by giving a single intravenous dose of the specific antigen shortly before cannulation of the thoracic duct, although the lymphocyte donors themselves respond normally. The injection of antigen does not decrease the output of lymphocytes in the thoracic duct and the effect is specific for the antigen injected. The findings are most readily accounted for by assuming that small subpopulations of specific lymphocytes are selected from the recirculating pool by antigen which has localized in lymphoid tissue. The observation that passive antibody abolishes selection by SRBC supports this interpretation. The strong selection exerted by a subcutaneous injection of SRBC in Freund's complete adjuvant, which induces delayed hypersensitivity but little early antibody, suggests that a common cell type may be involved in the induction of both delayed hypersensitivity and antibody formation. The anti-DNP antibody response generated by TDL from rats immunized with DNP BGG was abolished by a selecting injection of the homologous conjugate. The response was depressed to a smaller degree by injections of either BGG or dinitrophenylated human serum albumin, suggesting that carrier-specific (T) and hapten-specific (B) lymphocytes could be separately selected from the recirculating pool. The regional selection of recirculating lymphocytes by antigen may explain a number of phenomena in which the prior injection of antigen has been found to inhibit a subsequent immune response.

Animals↗