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At least 523 records · Page 29Linked to original sources
PubMed1988

Histological changes of bile duct in experimental graft-versus-disease across minor histocompatibility barriers. III. Immunoelectron microscopic observations.

Graft-versus-host disease (GVHD) was produced by injecting lymphoid cells from B10.D2 mice into BALB/C mice. Both are H-2-identical but differ only at multiple minor H loci. The expression and localization of MHC class II antigens on the bile duct epithelium was examined using an immunoelectron microscopical method. All GVHD mice developed bile duct lesions of chronic nonsuppurative cholangitis and expressed MHC class II antigens on their bile duct epithelium, while none of the control mice, which injected with the same number of syngeneic lymphocytes, developed bile duct lesions or expressed the antigens. The antigenic expression was characteristically localized on the basolateral surface of the bile duct epithelium but not on the apical surface. Furthermore, the expression varied markedly in its intensity and distribution within the same liver and even within a single bile duct. The infiltration of Lyt-1-positive helper/inducer lymphocytes in the duct epithelial layer apparent by electron microscopy was predominant to a much degree than that of Lyt-2-positive cytotoxic/suppressor lymphocytes and non-lymphocytic cells. The immunological mechanisms involving helper/inducer T cells in association with MHC class II antigens on bile duct epithelium may be important in the induction and progression of the bile duct lesions apparent in the present GVHD model.

Animals↗
PubMed1983

Elimination of allogeneic lymphocytes by mice.

Two major classes of response to allogeneic lymphocytes can be detected in mice in vivo, based on injecting them intravenously with 51Cr-labelled lymph node cells and examining them in a short term assay. A natural immunity discriminating between allogeneic and syngeneic lymphocytes is seen in the lymph nodes (and to a lesser extent, the spleen), which has such close similarities to natural cell-mediated responses of the NK class as thymic-independence and radioresistance. However, it has immunological specificity of a conventional kind, probably towards serologically determined K/D antigens. There is also an active immune response, produced by immunisation with dissociated lymphoid cells or allografting, which consists of three elements: an IgG opsonising alloantibody response, diverting circulating lymphocytes to the liver; an IgM opsonin, localising them to the spleen; and a cell-mediated serum-dependent elimination mechanism that destroys cells entering the lymph nodes and spleen. Dose-response curves for the primary response show evidence of high-dose paralysis of elimination. Dose-time-response results for the secondary show a variety of unique characteristics; evidence is presented to suggest that several aspects of the phenomenon betray primitive features retained from an earlier stage in the evolution of the immunological system.

Animals↗
PubMed1983

Natural cytotoxicity: early killing of allogeneic lymphocytes in rats.

In many strain combinations among inbred rats, intravenously injected 51Cr-labelled lymphocytes are destroyed in substantial numbers by unsensitized allogeneic hosts. Destruction of cells (referred to as natural cytotoxicity (NC)) occurs within a few hours of injection, and is characterised by a decreased accumulation of radioactivity in the lymph nodes and increased renal excretion of label by allogeneic hosts, as compared with the distribution of label in syngeneic recipients of the same cell suspension. An intact spleen is necessary for killing. The level of NC expressed is consistent for a given donor-host combination. Using arbitrary criteria to compare the levels of NC expressed by different donor-host combinations among inbred rats, 13 of 95 strain combinations have been shown to express high NC, 63 intermediate NC and 19 low NC. The level of NC expressed cannot be correlated with the extent to which donor and host differ in respect of known MHC genes. Segregation analysis has shown high NC to be controlled by at least 2 independently segregating genes, one of which is MHC-linked. It is possible to weaken or abrogate NC by the neonatal injection of bone-marrow cells from the donor strain, and to reverse this reduced reactivity by the injection of host strain lymphocytes. The substitution of either the donor (P1) or the host (P2) by the P1 X P2)F1 hybrid reduces or eliminates NC in strain combinations normally expressing high NC. It is currently uncertain whether NC can be augmented. In the single strain combination in which maturation has been studied, NC becomes evident during the 4th week of life and attains adult levels during the 6th-7th weeks. NC is at least partially radio-sensitive. Two groups of reactivities appear to be related to NC: (i) those which have been identified in the context of aberrant lymphocyte homing, and for which allogeneic lymphocytes are the targets; (ii) the group of natural resistance systems which includes NK cells, and whose reactivity is directed against a variety of other target cells.

Animals↗
PubMed1983

Lymphocyte migration across major histocompatibility barriers in splenectomized rats.

Localisation and migration patterns of iv injected radio-labelled thoracic duct (TD) lymphocytes were studied in particular with regard to passage through lymph nodes and re-entry into thoracic duct lymph. To avoid unwanted splenic sequestration of migrating lymphocytes presenting alloantigens to the recipient, only splenectomized recipients were used. Donor cells and recipients differed at the MHC (RT-1) locus, either in fully allogeneic (AO -- greater than BN and v.v.) or semi-allogeneic (AO -- greater than AO X BN and v.v.) combinations. In two of these combinations (BN -- greater than AO and AO X BN -- greater than AO) deficient output in TD lymph correlated with deficient localisation in lymph nodes and high amounts of radioactivity in the liver. In the other allogeneic combination (AO -- greater than BN), however, high TD output (i.e. when compared with the syngeneic combination BN -- greater than BN) correlated with good localisation in lymph nodes and low (control) levels of radioactivity in the liver. It was postulated that lymphocyte migration from blood to lymph under these circumstances can only be studied as an artifact secondary to whether or not migrating cells are removed from the circulation before they can reach and cross HEV's. These Allogeneic (or Altered) Lymphocytes Removing Tissues (by definition: Extranodular) may (conceptually) be comprised within one system: ALERT. It is our working hypothesis that the study of lymphocyte migration across (major) histocompatibility barriers is seriously impaired by the functioning of ALERT. It might be worthwhile to try and create conditions in which interference by this system is prevented, e.g. by using tolerant animals or bone-marrow chimeras.

Animals↗
PubMed1983

The rapid elimination of allogeneic lymphocytes: relationship to established mechanisms of immunity and to lymphocyte traffic.

Allogeneic lymphocyte cytotoxicity (ALC) refers to the destruction of lymphocyte beginning within a few hours of intravenous injection into non-sensitized, allogeneic recipients. Usually this has been detected in rats and mice by comparing the localization of 51Cr-labelled lymphocytes in the tissues of allogeneic and syngeneic recipients. In a particular strain combination the existence of ALC is supported by deficient localization of allogeneic lymphocytes in the LN, lungs and blood mononuclear population and an excess of the label that had been associated with allogeneic cells in the lymph plasma, blood plasma and kidneys. As the destruction of the allogeneic cells occurs in the lymphatic tissues, especially the spleen, it is paradoxical that there is sometimes an excess of the label associated with allogeneic cells in the spleen but evidence is presented that most of the isotope is no longer associated with living cells in that organ at 24 h after transfer. The data cannot be explained by an altered distribution of allogeneic lymphocytes between different organs. Experiments on the early migration of lymphocytes from the blood of syngeneic and allogeneic recipients point unequivocally to the conclusion that the adhesion of lymphocytes to specialized vascular endothelium in LN and their consequent entry into LN does not require that the lymphocytes and the endothelial cells share MHC products. The characteristics of ALC stressed in this review include the following: 1) it is independent of T-cell activation, either of host T-cells or of donor T-cells: 2) B- and T-cells are about equally vulnerable to ALC; 3) it varies greatly between different strain combinations regardless of other indices of cellular and humoral immunity; 4) F1 hybrid donor cells are vulnerable but the effect is always less marked than with allogeneic cells; 5) ALC is less radio-sensitive than primary cellular or humoral immune responses; 6) adoptive transfer of ALC can be achieved with TDL from nude rats. The possible mechanism underlying ALC has been debated in terms of natural killer cells recognizing certain allo-antigens or alternatively pre-existing "natural" antibody with low affinity for allogeneic cells leading to their elimination by ADCC. The argument hinges on the necessity for antibody and cannot be resolved by current data.

Animals↗
PubMed1991

Phenotypic and functional studies of human peripheral blood lymphocytes engrafted in scid mice.

CB.17 mice homozygous for the scid defect have been used as recipients of peripheral blood lymphocytes (PBL) from normal humans and from patients suffering from common variable immunodeficiency (CVI) types A and B. Following intra-peritoneal injection of PBL, such mice become chimeric with human cells, as evidenced by the presence in their serum of human immunoglobulins, which persist for a number of months. Under these conditions, B cells from CVI patients are also triggered to produce immunoglobulin. In contrast, T cells in the inocula, although they persist for 1 or 2 months in the peritoneal cavity, do not appear to function normally in antigen-specific responses and they do not recirculate in the recipient mice.

Animals↗
PubMedDate not supplied

Cell-mediated immune response in the mammary gland of guinea pigs adoptively sensitized with lymphocytes.

Guinea pigs were vaccinated intramammarly (IMM) with attenuated Mycobacterium bovis (BCG) and challenged intramammarly and intradermally with tuberculin. A significant (p less than 0.05) milk leukocytosis, consisting primarily of polymorphonuclear leukocytes, occurred from 6-30 hr after challenge with tuberculin. Intradermal challenge with tuberculin produced typical delayed-type hypersensitivity cutaneous reaction in these animals. Normal guinea pigs were adoptively sensitized with lymphoid cells from the inguinal lymph nodes or spleen of BCG-vaccinated animals and subsequently challenged intramammarly and intradermally with tuberculin. The mammary and dermal responses of the lymphoid cell recipients were similar to, but less pronounced, than those in the actively immunized animals. The responses in the recipients of lymphocytes from donors injected with tuberculin 18 hr prior to cell collection were greater than those from injected donors. Guinea pigs that were injected intraperitoneally with serum from BCG-vaccinated donors did not express significant dermal or mammary responses to subsequent challenge with tuberculin. It was proposed that the milk leukocytosis was mediated by sensitized lymphocytes stimulated by IMM challenge with tuberculin.

Animals↗
PubMed1986

Graft-vs-host reaction induced by para-aortic lymph nodes during estrous and diestrous stages.

Mouse uterine draining lymph node (UDLN) cells, or soluble factors released by them in both phases of the estrous cycle were examined in the graft-vs-host (GVH) assay. The immune response during the estrous phase was significantly decreased as compared with diestrous phase; 24-hour culture supernatant of UDLN cells was also able to decrease GVH activity mounted in F1 hybrids. This difference in reactivity was not found when peripheral nodes (PN) or spleen cells were tested. These results show that in physiological conditions it is possible to detect an hormonal influence on T lymphocyte function and would suggest that a non-specific immunosuppression would appear even during the estrous phase.

Animals↗
PubMed1993

Treatment of recurrent spontaneous abortion by immunization with paternal lymphocytes: results of a controlled trial.

PROBLEM: It remains unclear whether maternal immunization with paternal lymphocytes prior to conception improves the reproductive outcome in women with recurrent abortion in whom all secondary causes have been excluded. METHOD: A double-blind placebo controlled trial was instituted in women with unexplained recurrent spontaneous abortion, comparing immunization with 400 million paternal to 400 million maternal (autologous) lymphocytes. The groups were compared in a paired sequential trials chart, by logistic regression, and, in addition, a meta-analysis of this and other published trials was carried out. RESULTS: The live birth rate among pregnancies in paired couples with paternal lymphocyte immunization was 68% compared to 47% in the women who received their own cells. The results bordered on, but did not achieve, statistical significance. The women in each group were thoroughly investigated to exclude known causes of recurrent pregnancy loss and appeared to have been well matched in all variables. Women with lymphocytotoxic antibodies against paternal lymphocytes were excluded. Unlike our previous study there was not association between the time to conception and the chance of a successful outcome. Indeed, the time to conception was relatively short, 12 wk in all groups. The meta-analysis supported an overall modest favorable experience with paternal cells. CONCLUSION: The study is consistent with a general trend favoring paternal over maternal lymphocyte immunization but reinforces the need for larger multicenter controlled trials as well as more detailed biological study in humans to understand the nature of the maternal-fetal interface and its breakdown.

Abortion, Habitual↗
PubMed1993

Influence of immunotherapy on antisperm antibody titer in unexplained recurrent aborters.

PROBLEM: The mechanism of the beneficial effect of immunotherapy for human reproductive wastage remains to be elucidated. Because some women with unexplained recurrent spontaneous abortion are immunized with their partner's lymphocytes, it is important to determine whether such immunization results in elevation or enhancement of immunity to spermatozoa, because antigenic cross-reactivity between lymphocytes and spermatozoa has been reported. METHOD: The present study was initiated to evaluate the changes in antisperm antibody titer and lymphocyte subsets after immunotherapy as compared to before immunotherapy. Antisperm antibody detection was performed by SpermCheck Assay, which is based on a modification of the immunobead test. Maternal lymphocyte subsets were analyzed in two-color flow-cytometric experiments. RESULTS: The percentage of antibody-positive sperm decreased significantly (P = 0.0008) after immunotherapy. The percentage of B(CD19+) cells (P = 0.0003), cytotoxic T(CD8+ and CD11b-) cells (P = 0.02) and the Th/Ts ratio (P = 0.005) decreased significantly, while suppressor T(CD8+ and CD11b+) cells increased significantly (P = 0.0002) after the immunotherapy. This suggests that cell-mediated immunosuppression was induced by immunotherapy. CONCLUSION: The data of the present study suggest that antisperm antibodies have potential for use as a marker for a deficiency in maternal genital tract immunosuppressor mechanisms and that immunotherapy could be an effective treatment for women with antisperm antibodies who have unexplained recurrent abortions.

Abortion, Habitual↗
PubMed1995

Alloantibody responses to antigens recognized by rabbit antitrophoblast antisera in trophoblast and mononuclear cell (MNC) membranes by primary aborting women before and after paternal leukocyte immunization.

PROBLEM: Because shared allogeneic antigens are expressed on peripheral blood lymphocytes, as well as trophoblasts, it has been proposed that lymphocyte transfusions may appropriately sensitize recurrent spontaneous aborters (RSA) to trophoblast and lead to pregnancy conservation. The degree to which these responses are affected by this treatment, however, has not been defined. METHOD: SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot analyses were used to study the alloantibody responses in RSA patients both before and after immunization with paternal leukocytes (MNC) against membrane proteins isolated from peripheral blood mononuclear cells (MNC), first trimester and full term chorionic villi (CV). RESULTS: A distinct set of antigens with apparent molecular weights of 32, 36, 41, 63, 65, and 85 kDa was identified in both MNC and trophoblast membranes by rabbit anti-trophoblast antisera. In addition, a 55 kDa protein was recognized by MNC membranes. Thirty-eight percent of primary RSA sera recognized this 55 kDa protein. After paternal MNC immunization, all primary RSA samples displayed increased reactivity or produced antibodies to this 55 kDa protein when compared with preimmunization sera. The protein was identified as MCP using a rabbit polyclonal anti-MCP antisera. In contrast, reactivity to the other antigens present in the membrane preparations decreased after paternal MNC immunization. CONCLUSION: Changes in immune reactivity in RSA patients after paternal MNC immunization suggest that immunization alters serum immune reactivity to MNC and trophoblast shared antigens.

Abortion, Habitual↗