Peritoneal adherent cell inhibit the generation of cytotoxic T lymphocytes with prostaglandin-mediated system.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to C Kubo.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
When spleen cells primed in vivo against allogeneic lymphoid cells were used as responder cells in secondary mixed lymphocyte cultures, a high degree of cytotoxicity was generated even in the absence of splenic adherent cells. However, removal of adherent cells from such primed responder spleen cells reduced the cytotoxicity to some extent. On the other hand, when these responder cells were transferred into the peritoneal cavity of irradiated syngeneic mice together with antigenic cells, unseparated responder cells generated a lower degree of cytotoxicity than did adherent cell-depleted responder cells. In an in vitro system, peritoneal adherent cells also suppressed the generation of cytotoxic T lymphocytes by unseparated responders; however they augmented the cytotoxic T lymphocyte generation by adherent cell-depleted responders. These adherent cell populations with augmenting activity became inhibitory when they coexisted. The mechanism of this inhibitory action remains unclear.
The psychosomatic aspects of skin disease were studied both clinically and experimentally, from the standpoint of immunology. We found that emotional stress has a great influence on the immune system, as was manifested in skin disease. Skin test in allergic patients significantly improved with autogenic training and relaxation. For clarification of the effects of autogenic training and relaxation, various parameters were simultaneously assessed during the treatment. The serum levels of histamine and dopamine-beta-hydroxylase fluctuated, as determined by the microvibration test. The levels of IgE and findings on the PK test varied only slightly. Before the onset of urticaria, there were changes in the life-style and considerable stress in daily life as well as exposure to an allergen. Using mice subjected to stress, the functions of T cells and macrophages were evaluated. Stress appeared to have a definite influence on the functions of these cells, as related to the important role of the immune system and skin. Thus, the role of stress in clinical disease must always be given consideration.
Primary in vivo production of antibody to sheep red blood cells (SRBC) was consistently suppressed in EL 4 tumor-bearing C57BL/6 mice, but the secondary response was not suppressed. This suppressed primary in vivo production of antibody was partially restored by systemic administration of Corynebacterium parvum. For investigation of the mechanism of the immunosuppression in tumor-bearing mice and the effects of C. parvum, the accessory cell function of adherent cells from tumor-bearing mice and C. parvum-treated tumor-bearing mice in in vitro cultures was studied. Peritoneal and splenic cells from tumor-bearing mice were less efficient in promoting in vitro production of antibody to SRBC by macrophage-depleted normal nonadherent cells than the adherent cells from normal mice. C. parvum treatment restored the accessory cell function of splenic adherent cells from tumor-bearing mice but not that of peritoneal cells. Furthermore, adherent cells from tumor-bearing mice did not show suppressive activity against the in vitro plaque-forming cell response.
Explore the source record for details and available documents.
Following priming with alloantigen in vivo, a secondary cytotoxic activity of AKR mice (H-2k) was generated by in vitro stimulation with the same alloantigen. Such secondary effectors could lyse not only targets of a sensitizing haplotype but also third-party targets unrelated to sensitizing or responding cells. Such cross-reactive cytotoxicity of AKR secondary effectors were demonstrated not only by stimulation with C57BL/6 (H-2b) cells but also with C3H/He (H-2k) cells. It was observed that such cross-reactive secondary cytotoxicity was mediated by T lymphocytes, and required protein synthesis in secondary culture. These results suggested the possibility that the antigen receptors on such secondary cytotoxic effector cells have different recognitive specificity from that on primary cytotoxic effector cells.
The radiosensitivity of immune responses to allogeneic tumor cells was compared. Delayed hypersensitivity as demonstrated by macrophage migration inhibition and antibody production as detected by immune adherence test were extremely radiosensitive. The radiosensitive nature of macrophage migration inhibition was in marked contrast to he radioresistance of the delayed footpad reaction. The generation of cytotoxicity was relatively radioresistant.
Specific cytotoxicity against histocompatibility antigens of a parental strain was induced in the spleens of sublethally irradiated F1 mice after intravenous transfer of lymphoid cells from another parental strain. Such cytotoxicity reached the highest level at 10 days after the transfer of 3 to 5 X 10(7) spleen cells and was ascribed to be T lymphocytes of donor parental origin. Secondary response of the generation of cytotoxicity was compared among in vivo rechallenge, in vitro MLC and transfer to irradiated F1 mice. Cytotoxicity was not so augmented by in vivo rechallenge. It may be attributable to early elimination of grafts. In in vitro MLC and transfer to irradiated F1 mice, the generation of cytotoxicity appeared earlier with higher magnitudes as compared to primary response. The transfer system to irradiated F1 recipients appears to be more suitable for analyses of the generation of cytotoxic T lymphocytes from memory cells than in vivo rechallenge.
Effects of thymectomy of various times after birth on cytotoxicity, delayed footpad reaction and antibody production were examined in 6 week old mice immunized intraperitoneally with chicken erythrocytes. Cytotoxicity and antibody production were abolished by thymectomy within 3 days after birth. Mice thymectomized at 5 days of age or later showed appreciable degrees of cytotoxicity and antibody production. On the other hand, a delayed footpad reaction could be elicited even in mice thymetocmized within 24 h after birth, although the degree of the reaction was reduced by such a treatment. Therefore, T cells responsible for delayed hypersensitivity were less thymus-dependent and required the presence of the thymus for a shorter period in their development that those responsible for cytotoxicity or antibody production.
Explore the source record for details and available documents.
While immunization with allogeneic spleen cells did not generate positive cytotoxic activity, it produced accelerated rejection of subsequent tumour grafts carrying the same H-2 antigen. No augmented generation of cytotoxicity was detectable by 51Cr-release assay in the host spleen cells, even in the presence of accelerated rejection of tumour allografts. However, augmented cytotoxicity was generated in mixed lymphocyte culture and in peritoneal lymphocytes after an intraperitoneal boost. These results indicate that while immunization with allogeneic spleen cells does not generate mature cytotoxic T lymphocytes (CTL) detectable by the present assay, it may produce premature CTL that rapidly differentiate into mature CTL after direct contact with antigen at the site of graft rejection. The inability to generate a high degree of cytotoxicity in the spleen cells may be ascribed to the early development of CTL at the rejection site. The relationship between accelerated rejection of allogeneic tumour grafts and delayed-type hypersensitivity reactions is also discussed.
Explore the source record for details and available documents.
Direct cytotoxicity raised at an early interval after immunization with chicken erythrocytes (CRBC) has been ascribed to O-positive, immunoglobulin (Ig)-bearing lymphocytes. Cytotoxicity of such effector cells was not affected by trypsinization. Cytotoxity was reduced by the treatment of effector cells with anti-IgG serum and complement or by the addition of anti-IgG serum to culture medium for cytotoxicity test. When the effector cells were treated with trypsin before cytotoxicity test, such procedures with anti-IgG serum did not affect their cytotoxicity. Ig molecules on cytotoxic T lympohcytes may not be an essential element for antigen recognition. This explanation may be supported by the fact that cytotoxicity against CRBC could be raised in 600 rad irradiation, thymus-cell transferred mice in the absence of antibody production.
Exposure to 600 rad of X-irradiation 3 h after primary immunization with chicken erythrocytes (CRBC) abolished the production of antibodies and the generation of killer T cells, but scarcely affected the induction of delayed footpad reactions. Exposure to irradiation 3 h after secondary immunization reduced only slightly the generation of killer T cells and reduced slightly or substantially the production of antibodies. Delayed reactions persisted for long periods after elicitation in irradiated, boosted mice. Cross-reactivity between CRBC and quail erythrocytes (QRBC) was very weak with respect to the cytotoxicity, antibody and delayed reaction raised after primary immunization. Those raised after secondary immunization with the homologous antigen showed some degrees of cross-reactivity to another antigen. The booster with QRBC in CRBC-primed mice augmented the response to CRBC with respsect to the induction of cytotoxicity and delayed footpad reaction, but only weakly affected the response with respect to the production of antibody. Therefore, effector cells of cytotoxicity and delayed footpad reaction showed greater degrees of cross-reactivity than antibody-producing cells during an anamnestic response. The cross-reactive response raised after secondary immunization was radioresistant with respect to cytotoxicity and delayed footpad reaction but radiosensitive with respect to antibody production. Cytoxicity to immunizing antigen was inhibited by the unlabelled homologous antigen. Cytotoxicity to a cross-reacting antigen was inhibited by the same cross-reacting antigen and also by an immunizing antigen. There may exist heterogeneous populations of cytotoxic lymphocytes with different abilities to recognize antigens.
Effects of whole body irradiation with 600 rad on delayed hypersensitivity, direct cytotoxicity and antibody production were examined in mice immunized with chicken erythrocytes (CRBC) or sheep erythrocytes (SRBC) in saline. Delayed footpad reactions to CRBC were not affected by the exposure to irradiation 3 h before or after antigenic stimulation. On the other hand, direct cytotoxic activities in spleen cells and antibody titres to CRBC were reduced by such exposures. Additionally, delayed footpad reactions to SRBC were not affected by the exposure to irradiation. Generation of effector cells responsible for delayed footpad reactions proved to be resistant to irradiation.
Immune responses were examined after immunization with chicken erythrocytes (CRBC) in mice. Cytotoxicity of spleen cells was assessed by the release of 51Cr from labelled target cells. (1) At early stages (day 4-7) after primary intraperitoneal immunization, direct cytotoxicity of spleen cells was raised efficiently in C57BL/6 and AKR mice, but not in C3H/He, SL and DDD mice. Delayed hypersensitivity and antibody production were raised to almost the same extent in all the strains at such periods. (2) Effector cells in direct cytotoxicity were theta-positive and IgG-positive, and glass-nonadherent and Nylon wool column-adherent. Effector cells in antibody-dependent cell-mediated cytotoxicity in the presence of antibody to CRBC were eliminated by treatment with anti-IgG serum, but not by treatment with anti-theta serum. (3) Cytotoxicity and antibody production were raised efficiently after intraperitoneal or intravenous immunization, but not after footpad immunization. On the other hand, delayed hypersensitivity developed most efficiently after footpad immunization.
Explore the source record for details and available documents.