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CBA/N mice harbour an X-linked B cell defect which is transmitted by CBA/N female mice to their hybrid male progeny. These mice mount normal responses to thymus-dependent (TD) and some thymus-independent (TI-1) antigens, while the response to TI-2 antigens is absent. Hapten-specific plaque-forming cell (PFC) responses to TD antigens can be blockaded by concomitant exposure of these mice to TI-2 antigens bearing the same hapten. This paper investigates in defective mice the blockade of their response to TNP3-LPS (trinitrophenylated lipopolysaccharide, a TI-1 antigen), imposed by DNP59-Ficoll (dinitrophenylated Ficoll, a TI-2 antigen). The effectiveness of the blocking agent, DNP59-Ficoll, differed in various inbred mouse strains: CBA/N × C3H/HeN F1 male > CBA/N female > CBA/N · C3H/HeN F1 female. The role of T cells in the observed hapten-specific blockade phenomenon was investigated using athymic CBA/N nude mice and a B cell tolerogen. Our findings indicate that T cell participation is not essential for the blockade of CBA/N PFC responses and they suggest that direct blockade of TI- and TD-responsive B cell populations is likely to occur. [ABSTRACT FROM AUTHOR]

CBA/N mice have an X-linked S-cell defect which prevents them from responding to non- mitogenic thymus-independent (T1-2) antigens such as haptenated Ficoll. The CBA/N mice do, however, respond to another group of thymus-independent (TI-2) antigens among which are haptenated liposomes. The F1 male progeny of CBA/N female mice express the same characteristics. Hapten-specific plaque-forming cell (PFC) responses to haptenated proteins (thymus-dependent, TD, antigens) by CSA/N mice and CBA/N × C3H/HeN F1 male mice can be blocked by concomitant exposure to TI-2 antigens bearing the same hapten. Simultaneous exposure to haptenated liposomes (TI- I antigen) and TD antigens, however, results in a synergistic response to the hapten if the antigens share common epitopes. The tripeptide-enlarged hapten dinitrophenyl-β-alanylgly- cylglycine (J), conjugated to phosphatidyl-ethanol- amine (PE) and incorporated into liposomal model membranes, was used throughout the experiments. In F1 male mice the moderate responses to TD antigens could be restored to values equivalent to those seen in F1 female mice. This adjuvant effect of haptenated liposomes is hapten-specific, time-dependent, and restricted to certain structural forms of the liposomes. [ABSTRACT FROM AUTHOR]

Delayed-type hypersensitivity measured as footpad swelling was studied in a large number of inbred mouse strains. A conjugate of bovine serum albumin (BSA) with the small 2.4-dinitrophenyl (DNP) hapten served to generate strong reactions, specific for the DNP group. Delayed hypersensitivity was produced with the DNP-BSA complex mixed with the cationic, surface active lipid. dimethyl dioctadecyl ammonium bromide (DDA). Great variation was observed in delayed hypersensitivity among different mouse strains. For convenience, the mice were classified into five groups, notably: non-, low, moderate, good and high responders. The highest responding animals were HALB/cJ mice, the lowest were PJJN and outbred nu/nu mice. No correlation was observed between 1-1-2 type and the intensity of the elicited reactions. [ABSTRACT FROM AUTHOR]

Mice were immunized i.e. with various enlarged haptens conjugated to bovine serum albumin and mixed with the cationic, surface active lipid, dimethyl dioctadecyl ammonium bromide (DDA). This immunization generated delayed-type hypersensitivity (DH) in these mice without detectable concomitant antibody formation. The DH was measured as footpad swelling. However, both direct and indirect hapten-specific PFC could be detected in peripheral lymph nodes and in spleens 4 days after a challenge injection. Although the adjuvant, DDA, promotes a strong cross-reactivity in DH between heterologous hapten--carrier complexes, the antibody-forming cells produced 4 days after challenge showed relatively high specificity for the immunizing hapten. This indicates only weak cross-reactivity at the anti-body-forming cell level co-existent with high cross-reactivity in DH expression to the same hapten-carrier complexes. These results are consistent with the possibility that B-cell receptors may be capable of expressing a greater degree of hapten specificity than T-cell receptors. It is tentatively concluded that Thelper cells participating in antibody formation may represent a subset of the T cells involved in DH. [ABSTRACT FROM AUTHOR]

Both nude mice (nu/nu) and their heterozygous littermates (nu/+) were injected with a single IP dose of 300 mg cyclophosphamide (CY)/kg. CY is a known immunosuppressive agent, which affects primarily B lymphocytes. Immunization with the thymus independent antigen DNP-AGG59- Ficoll after CY treatment disclosed that restoration of the primary direct PFC response occurred more rapidly in nude mice than in nu/+ mice. However in these same experiments, the primary indirect PFC response, recovered earlier in nu/+ mice than in nude mice. After CY treatment, secondary indirect PFC responses were delayed in both nude and nu/+ mice, but the greatest effect was seen in nude mice. The data suggest that the presence of T cells has little if any influence on the recovery capacity of those B cells which are destined to become direct PFC. However the recovery of B cells which are destined to produce indirect PFC responses is facilitated by the presence of T cells. [ABSTRACT FROM AUTHOR]

Murine monoclonal antibody (MAb) 225 (IgG1) against the epidermal growth factor (EGF) receptor competitively blocks EGF binding and inhibits EGF-induced activation of receptor tyrosine kinase and cell proliferation. The effect of MAb 225 was studied in a phase I trial in patients with inoperable squamous cell carcinoma of the lung, which invariably expresses high levels of EGF receptors. Groups of three patients received total doses of MAb 225 ranging from 1 mg to 300 mg. Except at the lowest dose, each infusion included 4 mg of indium 111 (In)-labeled MAb 225. No toxicity was observed. Tumors were imaged in all patients who received doses of 20 mg or greater. Presumed metastases greater than or equal to 1 cm in diameter were imaged with doses of 40 mg or greater. Single-photon-emission-computed tomography could be carried out at the 120-mg and 300-mg doses and significantly improved tumor visualization. All patients produced anti-murine antibodies. We conclude that treatment with an MAb that inhibits EGF receptor function is safe at the doses and schedule studied. In-labeled MAb images squamous cell lung carcinoma; tumor uptake of the labeled MAb is dose dependent. Further studies are warranted to explore the potential therapeutic efficacy of anti-EGF receptor MAbs and other agents that act in a comparable manner. [J Natl Cancer Inst 83:97–104, 1991] [ABSTRACT FROM PUBLISHER]

Delayed-type hypersensitivity (DH) in the mouse was provoked with different haptencarrier complexes mixed with the cationic, surfaceactive lipid, dimethyl dioctadecyl ammonium bromide (DDA). DH was measured as footpad swelling.Conjugates of bovine serum albumin (BSA) with the small haptens dinitrophenyl (DNP), 'arsonate'(ARS) and 'sulphonate' (SULPH) served to generate strong DH reactions towards the homologous antigen. Insertion of a tripeptide spacer between the hapten and carrier resulted in lower DH reactivity. Optimal dosages and optimal time intervals between sensitization and DH elicitation were determined for the enlarged hapten-carrier complexes. Cyclophosphamide (CY) treatment, before priming with complexes mixed with DDA, caused a 5-6 day delay in the expression of DH but failed to evoke enhanced DH for any of the antigens tested. A broad array of cross reactions between small and enlarged hapten-carrier complexes showed a relative lack of specificity in these DH responses. The results are compared with others reported in the literature and are explained mainly by the effects of electrostatically bound lipid groups of DDA in the sensitizing conjugates. [ABSTRACT FROM AUTHOR]

Investigates the influence of synthetic polymeric agents on the immune responsiveness of congenitally athymic nude mice by determining the effects of in vivo treatment with polynucleotides and polymeric haptenated antigens on splenic theta-bearing cells. Cell responses to thymic dependent and thymic independent antigens; Absence of acquisition of improved T-cell function in nude mice.