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Mice injected i.v. with corresponding transplantation sera (containing anti-H-2 antibodies) exhibited severe (often fatal) shocks occurring in the subsequent 20 min. Accompanied by deep hypothermia, followed by a refractory period, these shocks were immunologically specific, and the corresponding serum activity was specifically removable by target antigens. Although inhibited by aggregated human γ-globulins (HGG), this “immunoallogeneic shock” was attributed to a reverse passive anaphylactic shock for the following reasons it was completely inhibited by Phenergan and it was consistently correlated with the anaphylactic properties of the sera utilized or their chromatographic fractions and not with their complement-fixing activity

Sera from guinea-pigs immunized with their own spermatozoa or with purified preparations of three different guinea-pig sperm autoantigens (S, P and T) were tested for their spermatotoxic and cytotoxic (towards immature sperm cells) properties in the presence of complement, as well as for their spermagglutinating properties. Autoimmune and anti-T sera exhibited the three properties with a high degree of tridimensional correlation. Anti-S and anti-P sera did not exhibit any of the three properties. The three properties could be specifically absorbed by T but not by S or P autoantigens. While P/anti-P and T/anti-T are both complement-fixing systems, only T is present at the cell surface and only anti-T will fix on living sperm cells. The biological and immunopathological consequences of the preceding results are discussed in relation to the ability of each one of the three sperm autoantigens to induce an autoimmune aspermatogenic orchitis.

Passive cutaneous anaphylactic (PCA) reactions are shown to be elicitable with an H-2 antigen-antibody system in mice. The solubility and innocuity of the antigenic preparations are important for the outcome of the reaction. H-2 anaphylactic activities can be separated from complement-fixing activities. The responsible antibodies were contained in either transplantation immune sera or serum fractions. They are related to electrophoretically fast migrating immunoglobulins of 7 S IgG class, reaginic antibodies not being involved in the reaction. IgG1antibodies are the best candidates as mediators of the reaction. However, a fast migrating portion of IgG2has not been excluded as a possible candidate. The use of this technique for analyzing the biological properties of transplantation immune sera is discussed.

CBA anti-A immune sera and their chromatographic fractions were tested for their biological activities in vitro and in vivo. In vitro methods comprised hemagglutination, lymphotoxicity, and immune hemolysis. Anaphylactic antibodies were evaluated by passive cutaneous anaphylaxis (PCA) reactions using solubilized H-2 antigens for i.v. injections. Facilitating properties were assessed by enhancement of Sal A/Jax tumors. Immune sera were studied either as whole sera raised by immunization procedures favoring the production of either anaphylactic or complement (C)-fixing antibodies or serum fractions obtained by chromatography procedures. A highly significant correlation between PCA and facilitating-enhancing activities was established in either system, whereas other biological activities seemed to be independent within the ranges tested. The role of non-C-fixing anaphylactic antibodies (IgG1) in immunological facilitation enhancement is strengthened and discussed.

Hybrid adult mice can be protected against wasting disease induced by spleen cells from parental origin, by utilizing the immunological enhancement-facilitation phenomenon. Passive enhancement-facilitation was applied using a “B anti-A” type of immune serum injected into (B X A)F1hybrids before the injection of B lymphoid cells. Active enhancement-facilitation was used in similar strain combinations by means of appropriate immunization of the prospective B spleen cell donors; typically the immunizing material consisted of extracts prepared from lyophilized A tissues (3 mg) and immunizing injections were made 5 clays before the donor spleens were transferred. (1) Passive enhancement-facilitation of (B1OD2 X CBA)F1hybrids receiving B1OD2 spleen cells, by means of an anti-CBA B1OD2 immune serum, increased survival rates from 1 to 13–40. This effect of the immune serum was removed by specific absorption. (2) Active enhancement-facilitation displayed its effect clearly in the same strain combination and also in the C57BL6 → (C57BL6 X CBA)F1combination, where specificity of the phenomenon was controlled in a group of hybrids receiving cells from parental donors immunized with extracts of guinea pig lyophilized tissues. (3) Varying immunization procedures or strain combinations had sometimes an opposite effect, resulting in an aggravation of the disease (sometimes limited to an increased lymphocytopenia). (4) The spontaneous hemagglutination phenomenon in Gorer-Mikulska's medium is described as a sign of antibody fixation at the surface of mouse erythrocytes. In the present experiments, it results from a graft-versus-host reaction.

The effect of passively administered IgG1 and IgG2 anticarrier antibodies on the IgG1 and IgG2 antihapten response has been studied. Guinea pigs were immunized with dinitrophenylated bovine gamma globulin mixed with purified IgG1 or IgG2 antihuman gamma globulin antibodies, i.e., antibodies directed against a limited range of the carrier determinants. Humoral IgG1 and IgG2 anti-DNP antibody contents were assayed at weekly intervals and 4 to 10 days after a booster injection of antigen in saline given on the 12th wk. The main finding was the sustained suppressive effect of passive IgG1 anti-carrier antibodies on the active IgG1 antihapten response. This result is compared with the enhancing effect of passive IgG1 antihapten antibodies and is discussed in the light of T cell-B cell and hapten-carrier relationships, leading to the proposal of a regulatory function of the Fc portion of the IgG1 anticarrier antibody, combined with the antigen, on the T cell.

CBA mice were rendered highly tolerant to A/Jax cells by neonatal intravenous injections of (CBA x A)F1 spleen cells. The high degree of tolerance was ascertained by the absence of circulating antibodies detected in the sera by the usual tests and by the perfect state of A skin grafts during all the experiments. Tolerant sera (sera from tolerant animals) were studied at three periods of tolerance: before skin test grafting, from 2 to 11 wk after grafting, and at time of sacrifice at almost 6 months of age. The tolerant sera were shown to have specific facilitation-enhancing properties promoting the take and growth of A/Jax sarcoma (SaI and /Sa 15091a grafted on normal CBA mice. These properties were present throughout the duration of the experiments, showing that they were not the result of a beginning interruption of tolerance. The tolerant sera, although lacking the usual serological properties (hemagglutination, hemolysis, cytotoxicity, passive cutaneous anaphylaxis) had, however, specific synergistic hemagglutinating properties (increasing the hemagglutinating titer of a reference immune serum). Antibodies giving direct specific hemagglutination could be extracted from spleens of 20% of highly tolerant mice. The tolerant sera were also found to contain more IgG1 and more IgA than normal sera while they contained normal quantities of the complement-fixing immunoglobulins IgG2 and IgM. Fractionation of tolerant sera on DEAE chromatography column confirmed the data concerning immunoglobulin classes and demonstrated direct specific serological activities undetected in unfractionated sera: a weak hemolysis in the most cationic fractions and a weak hemagglutination in the middle fractions. Synergistic hemagglutination, detected in unfractionated serum, was localized in fast anionic fractions containing high IgA concentration, along with facilitation-enhancing activity, thus confirming a link suggested previously between these three properties. The relation between immunological tolerance and facilitating antibodies was discussed in the light of the fact that antibodies, possibly of a particular class continuously present at low dose in the sera of highly tolerant animals, are able to transfer (at least partly) this state of tolerance provided a sensitive test system is utilized.