Induction of immunocellular resistance to IL-2-activated lymphocytes within ovarian carcinoma cells.

The development of resistance within ovarian carcinoma cells to activated cytotoxic lymphocytes was the objective of this study. Primary ovarian carcinoma cells were obtained from the ascites of a patient. These cells were cocultured with IL-2-activated autologous tumor-associated lymphocytes (TALs) for 1 week.

Induction of foetal lethality in AKR offspring after repeated inoculations into AKR females of anti-TCR/V beta 6 monoclonal antibody.

Female AKR (H-2k, Mlsa) mice were repeatedly injected with monoclonal anti-V beta 6 prior to and during syngeneic pregnancy. The offspring were born non-viable or died within 24 h. Continued injections into the mother resulted in abortions and conception eventually ceased altogether.

Anti-Mlsa-like effect of CBA/J anti DBA2 antibody in in vitro MLRs between Mls incompatible combinations.

Antisera from CBA/J (H-2k,Mlsa) mice hyperimmunised with DBA2 (H-2d,Mlsa) and/or AKR (H-2k,Mlsa) splenocytes, can block in vitro MLRs against Mlsa determinants. These two antisera are furthermore specifically cytotoxic against targets expressing H-2 components but not against Mlsa-bearing targets. In these experimental models the anti-Mlsa-like effects of CBA/J anti-DBA2 and CBA/J anti AKR antibodies seem to be associated with an autoreactive immune response in CBA/J mice elicited by DBA2 and AKR splenocytes, respectively.

Anti-T-cell receptor V beta 6 breaks tolerance in Mlsa mice and induces production of anti-Mlsa antibodies.

Tolerance to the minor lymphocyte stimulating (Mls) self-antigens has been shown to be due to the intrathymic deletion of T-cell clones bearing certain T-cell receptor (TcR) V beta regions. T cells bearing these V beta regions (V beta 6, V beta 7, V beta 8.1, V beta 9) are deleted in Mlsa-positive mice.

Murine hybridomas secreting monoclonal antibodies reacting with Mlsa antigens.

Murine monoclonal antibodies have been developed from spleens of AKR mice hyperimmunised with the monoclonal antibody against TCR-V beta 6. Two new monoclonal antibodies called AL-12-3 and AL-32-7 were able to specifically block Mlsa-induced but not MHC-induced mixed lymphocyte responses in a dose-dependent manner. Both antibodies are mouse IgG3 lambda chain isotype and bind to Mlsa-bearing lymphocytes from different strains of mice.

Anti-TCR-V beta 6 breaks tolerance in female AKR, Mlsa mice inducing foetal lethality.

Immunisation with anti-TCR-V beta 6 of female AKR mice prior to and during syngeneic pregnancy resulted in neonatal lethality and eventually in abortion or foetal resorption. The sera of the hyperimmunised mothers were shown to have anti-H-2k and anti-Mlsa autoantibodies and were cytotoxic to H-2k targets in vitro and also blocked Mlsa-induced mixed lymphocyte reactions. These observations are discussed herein.

Cellular mechanisms of graft-versus-host disease in a mouse model.

Female CBA/H (H-2k, Mlsb) mice alloimmunized prior to and during syngeneic pregnancy with DBA/2 (H-2d, Mlsa) splenocytes gave rise to offspring which resisted graft-versus-host disease (GVHD) following neonatal intraperitoneal inoculation of high doses of DBA/2 spleen cells. Lymphocytes from GVHD-resistant mice tested after 6 weeks of age were unresponsive to DBA/2 stimulator cells in 72 h mixed lymphocyte cultures. Isotope uptake measured 24 h after culture, however, indicated that a considerable early response was made to DBA/2 which later declined.

Unresponsiveness to Mlsa induced in newborn Mlsb mice by maternal preimmunization.

Female BALB/c (H-2d, Mlsb) mice alloimmunized prior to and during syngeneic pregnancy with DBA/2 (H-2d, Mlsa) splenocytes gave rise to offspring with severely reduced responsiveness in adult life to DBA/2 stimulation in vitro mixed lymphocyte cultures. The offspring of the hyperimmunized mothers were also tolerant to neonatal challenge with large numbers of DBA/2 splenocytes, which resulted in runting disease of control neonatal BALB/c mice. Both challenged and unchallenged offspring of the immunized BALB/c mothers were hyporesponsive to DBA/2 but both stimulated and responded to normal BALB/c lymphocytes, indicating alteration in their T-cell repertoire.

Protection of newborn mice from graft versus host disease by maternal pre-immunization.

Alloimmunization of BALB/c (H-2d) female mice with allogeneic spleen cells from C57BL/6 (H-2b) or CBA/H (H-2k) mice protects BALB/c offspring from graft-versus-host disease (GVH-D) following neonatal intraperitoneal inoculation of high doses of spleen cells respectively of C57BL/6 or CBA/H strains of mice. The mice survived GVH-D over one year after the allogeneic inoculum 24-48 h after birth and they did not show any signs of GVH reaction nor splenomegaly. We show that this phenomenon is antibody mediated and affects the developing immune system of the foetus.

Reduction of graft-versus-host disease in neonatal F1 hybrid mice.

Pre-immunization of BALB/c (H-2d) mothers with C57BL/10 (H-2b) or CBA/H (H-2k) spleen cells partially protected the F1 hybrid offspring of (BALB/c x C57BL/10) or (BALB/c x CBA/H) matings from graft-versus-host-disease (GVHD) induced by neonatal intraperitoneal inoculation with spleen cells of the paternal strain. The effects achieved were manifest as a reduction in mortality. Experiments to establish whether the phenomenon was antibody mediated were performed by passive pre-immunization of BALB/c mothers with alloantisera obtained from BALB/c previously immunized with C57BL/10 spleen cells.

Tumour necrosis factor-alpha enhances the cytolytic and cytostatic capacity of interleukin-2 activated killer cells.

The cytotoxic and cytostatic responses of peripheral blood lymphocytes from eight cancer patients and splenocytes from four patients activated with rIL2 and a combination of rIL2 and rTNF-alpha were tested against two tumour cell lines. The cytotoxic response of rIL2-activated lymphocytes did not exceed the natural killer cytotoxicity values in all patients tested. In fact the killing capacity of some PBL deteriorated after rIL2 activation.

Modulation and biological effects of Ly-6.2 expression on EL4 tumour cells.

EL4 tumour cells maintained in culture were separated by FACS analysis to Ly-6.2 negative and Ly-6.2 positive subsets.

Human cytotoxic T-cells against measles virus-infected and myelin basic protein-coated targets are cross-reactive.

Cytotoxic T lymphocytes (CTL) which recognized measles virus antigens were generated by in vitro sensitization of peripheral blood lymphocytes from normal volunteers against autologous measles virus-infected lymphocytes. Cytotoxicity of measles virus-infected targets by these effectors was considerably enhanced when the effector-target cell mixtures were incubated in presence of 10 or 100 ng myelin basic protein (MBP) for the 3-hour duration of the 51Cr release assay. In most experiments, specific release of radioisotope was doubled or tripled.

Association of the lymphoproliferative disease inducer gene Arp with autoimmunity and resistance to tumour growth.

This report describes a biological role for the diallelic gene system, Arpa and Arpb, which codes for surface antigens on murine lymphocytes and tumour cells. Arpb is present only in a mutant strain of BALB/c which is designated BALB/c-Arpb. Normal BALB/c and all other strains of mice tested express Arpa.

Characterization of cytostatic effector lymphocytes during the development of a syngeneic lymphosarcoma in C3H mice: use of monoclonal reagents to identify T-cell subsets.

The development of the in vitro cytostatic capacity of splenic lymphocyte subpopulations from C3H mice carrying the syngeneic Gardner tumor was examined at different times after intramuscular tumor injection. Most mice died between 3 to 6 weeks after tumor injection, while some rejected their tumors or survived longer than 3 months. Cell separation procedures and monoclonal antibodies against T-cell subsets were used to identify the cells responsible in anti-tumor immunity.

Alloimmune interactions of a lymphoproliferative disease-inducer gene Arp and linkage to Pep-7.

In this report we describe a new diallelic gene system, Arpa and Arpb, which codes for surface antigens on murine lymphocytes. Arpb is present only in a mutant strain of BALB/c which is designated BALB/c-Arpb. Normal BALB/c and all other strains of mice tested express Arpa.

Differential sensitivity of lymphocyte subsets to corticosteroid treatment.

Corticosteroid treatment of SJL mice produced a marked decrease in the number of viable lymphocytes obtained 48 hr later from the thymus, spleen and lymph node but no change in peripheral blood. Within the residual lymphocyte population there was a fall in the relative number of splenic B cells with increasing dose; in contrast the proportion of B cells increased in the lymph nodes. The most marked change however was a dose-related increase inthe Lyt-2+ population in all of the lymphoid organs examined including the thymus though, in this organ alone, the lowest dose caused a pronounced reduction in the Lyt-2+ population, since most immature thymocytes are Lyt-2+.

Molecular weight determination of two genetically linked cell surface murine antigens: ThB and Ly-6.

Various murine tumor lines were screened by FACS analysis for the surface antigens ThB and Ly-6.2. Positive cell lines were used for immunoprecipitation studies.

H-2d-like specificities on Gardner (H-2k) tumour detected in a restricted anti-tumour reaction.

Cytostatis of the H-2d tumour LSTRA by H-2-restricted effector lymphocytes was inhibited by antisera against H-2.4 and H-2.31 but not by antisera against public specificities or non-H-2 antigens.

Contrasting effects of H-2 and Mls immunization on the polyclonal mitogenicity of murine lymphocytes.

During the immune response to H-2 and Mls alloantigens, murine lymphocytes showed altered sensitivity to polyclonal mitogens. The reactivity to the T-cell mitogen PHA followed a similar pattern in both H-2 and Mls-immunized mice while the reactivity to the B-cell mitogen LPS was contrasting in the two groups. In the former group, the response exceeded control levels by the seventh day after immunization and then gradually dropped below control levels; the response of Mls-immunized lymphocytes dropped below control levels soon after immunization and remained so for the period of study.