Cellular events in protein‐tolerant inbred rats

The ability of immunogens to maintain or extend a state of unresponsiveness was investigated in unbred rats using a human serum albumin (HSA) model of tolerance. Rats initially challenged with immunogen within two weeks of high or low dose tolerance induction by tolerogen (soluble HSA) remained hypore‐sponsive even a year and a half later and in some cases became less responsive following a subsequent challenge. An inhibitory effect of immunogen on escape from tolerance was formally demonstrated: in comparison with an unchallenged group, tolerant rats which received a second immunogen challenge 6 months after the first, synthesized less antibody; this antibody underwent a gradual decline in affinity after each challenge which suggested that higher avidity B cells were progressively lost. In addition, immunogen‐maintained tolerant rats (a) had demonstrable helper T cell activity among their thoracic duct lymphocytes on adoptive transfer, (b) did not produce a significant increase in antibody synthesis after receiving peripheral T cells and (c) provided no evidence that suppressor cells were playing a role. The results suggested that the mechanisms of tolerance induction by tolerogen and tolerance maintenance by immunogen are fundamentally different.

[1]  C. Elson.  Tolerance in differentiating B lymphocytes , 1977, European journal of immunology.

[2]  A. Coutinho,et al.  Spleen cells from animals tolerant to a thymus-dependent antigen can be activated by lipopolysaccharide to synthesize antibodies against the tolerogen , 1976, The Journal of experimental medicine.

[3]  E. Metcalf,et al.  In vitro tolerance induction of neonatal murine B cells. , 1976, The Journal of experimental medicine.

[4]  D. E. Parks,et al.  Specific suppression of the immune response by HGG tolerant spleen cells. I. Parameters affecting the level of suppression. , 1976, Journal of immunology.

[5]  M. Feldmann,et al.  Mechanisms of B-cell tolerance. , 1976, British medical bulletin.

[6]  E. Bell,et al.  Persisting T cells in rats tolerant of human serum albumin. The significance of tolerant and nonimmune T cells which preferentially restrict high affinity antibody synthesis , 1975, European journal of immunology.

[7]  A. Coutinho,et al.  Hapten‐induced B cell paralysis. II. Evidence for trivial mechanisms of tolerance , 1975, European journal of immunology.

[8]  T. Amagai,et al.  Tolerance induction in TxXBT and TxXB mice. , 1975, Immunology.

[9]  J. Schrader.  Tolerance induction in B lymphocytes but thymus-dependent antigens. T cells may abrogate B-cell tolerance induction by prevent an antibody response , 1975, Journal of Experimental Medicine.

[10]  D. Benjamin.  Evidence for specific suppression in the maintenance of immunologic tolerance , 1975, The Journal of experimental medicine.

[11]  C. Elson,et al.  Permanent hapten-specific tolerance in B lymphocytes. , 1975, Immunology.

[12]  E. Ruoslahti,et al.  Changes in lymphocytes recirculation and liberation of the adoptive memory response from cellular regulation in irradiated recipients , 1975, European journal of immunology.

[13]  J. Howard,et al.  Induction of B cell tolerance to polysaccharides by exhaustive immunization and during immunosuppression with cyclophosphamide , 1974, European journal of immunology.

[14]  J. Sprent,et al.  CELL-TO-CELL INTERACTION IN THE IMMUNE RESPONSE , 1974, The Journal of experimental medicine.

[15]  Y Borel,et al.  The tolerant cell: direct evidence for receptor blockade by tolerogen. , 1974, Journal of immunology.

[16]  K. Rajewsky,et al.  Paralysis to serum albumins in T and B lymphocytes in mice. Dose dependence, specificity and kinetics of escape , 1974, European journal of immunology.

[17]  J. Louis,et al.  THE ABILITY OF BACTERIAL LIPOPOLYSACCHARIDE TO MODULATE THE INDUCTION OF UNRESPONSIVENESS TO A STATE OF IMMUNITY , 1973, The Journal of experimental medicine.

[18]  M. Cohn,et al.  THE USE OF BACTERIAL LIPOPOLYSACCHARIDES TO SHOW THAT TWO SIGNALS ARE REQUIRED FOR THE INDUCTION OF ANTIBODY SYNTHESIS , 1973, The Journal of experimental medicine.

[19]  J. Chiller,et al.  Induction of immunological tolerance in neonatal and adult rabbits. Differences in the cellular events. , 1973, Cellular immunology.

[20]  E. Bell.  Cellular events in protein tolerant inbred rats. II. Antibody avidity maturation during induction and loss of tolerance , 1973, European journal of immunology.

[21]  I. Mcconnell,et al.  Cellular events in protein tolerant inbred rats. I. The fate of thoracic duct lymphocytes and memory cells during tolerance induction to human serum albumin , 1973, European journal of immunology.

[22]  J. Chiller,et al.  Restoration of Immunocompetency in Tolerant Lymphoid Cell Populations by Cellular Supplementation , 1973, The Journal of Immunology.

[23]  N. Rose.  Cell Interactions and Receptor Antibodies in Immune Responses. , 1973 .

[24]  M. Feldmann.  INDUCTION OF IMMUNITY AND TOLERANCE IN VITRO BY HAPTEN PROTEIN CONJUGATES , 1972, The Journal of experimental medicine.

[25]  J. Ivanyi,et al.  Cellular mechanisms of escape from immunological tolerance. , 1972, Immunology.

[26]  D. Katz,et al.  CARRIER FUNCTION IN ANTI-HAPTEN ANTIBODY RESPONSES , 1971, The Journal of experimental medicine.

[27]  G. Habicht,et al.  Kinetic Differences in Unresponsiveness of Thymus and Bone Marrow Cells , 1971, Science.

[28]  S. Kawaguchi.  Studies on the induction of immunological paralysis to bovine gamma-globulin in adult mice. I. The competition between immunogen and paralytogen. , 1970, Immunology.

[29]  F. Celada,et al.  Determination of avidity of anti-albumin antibodies in the mouse. Influence of the number of cells transferred on the quality of the secondary adoptive response. , 1969, Immunology.

[30]  W. Weigle,et al.  Studies on the induction of immunologic unresponsiveness. 3. Antigen form and mouse strain variation. , 1969, Journal of immunology.

[31]  E. Sercarz,et al.  The X-Y-Z scheme of immunocyte maturation. II. The effect of antigen on spontaneous escape from immune paralysis. , 1967, Journal of immunology.

[32]  J. Šterzl.  Immunological Tolerance as the Result of Terminal Differentiation of Immunologically Competent Cells , 1966, Nature.

[33]  J. Humphrey.  IMMUNOLOGICAL UNRESPONSIVENESS TO PROTEIN ANTIGENS IN RABBITS. I. THE DURATION OF UNRESPONSIVENESS FOLLOWING A SINGLE INJECTION AT BIRTH. , 1964, Immunology.

[34]  H. Claman.  TOLERANCE TO A PROTEIN ANTIGEN IN ADULT MICE AND THE EFFECT OF NONSPECIFIC FACTORS. , 1963, Journal of immunology.

[35]  D. Dresser.  Specific inhibition of antibody production. II. Paralysis induced in adult mice by small quantities of protein antigen. , 1962, Immunology.

[36]  E. Bell,et al.  Cellular events in protein-tolerant inbred rats. III. Antigen-reactive B cells in rats tolerant to human serum albumin. , 1976, Cellular immunology.

[37]  D. Katz,et al.  Immunological tolerance; mechanisms and potential therapeutic applications , 1974 .

[38]  C. Elson,et al.  TOLERANCE IN ISOLATED B-CELL POPULATIONS IDENTIFIED BY AN ALLOTYPE-MARKER: ROLE OF T-CELLS IN INDUCTION , 1974 .

[39]  J. Fidler,et al.  IMMUNOLOGICAL TOLERANCE TO A HAPTEN I. INDUCTION AND MAINTENANCE OF TOLERANCE TO TRINITROPHENYL WITH TRINITROBENZENE SULFONIC ACID , 1973 .

[40]  M. Feldmann,et al.  Antibody-mediated suppression of the immune response in vitro. IV. The effect of antibody fragments. , 1972, Journal of immunology.

[41]  G W Siskind,et al.  Cell selection by antigen in the immune response. , 1969, Advances in immunology.

[42]  N. Mitchison,et al.  The mechanism of immunological paralysis. , 1968, Advances in immunology.

[43]  J. Ivanyi,et al.  The immunological significance of taxonomic origin of protein antigen in chickens. , 1966, Folia biologica.

[44]  J. Cerny,et al.  The effect of protein antigen dosage on its elimination from the blood and organs. , 1965, Folia biologica.

[45]  Richard T. Smith.  Immunological Tolerance of Nonliving Antigens , 1961 .