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At least 613 records · Page 34Linked to original sources
PubMed2006

Precursor frequency, nonlinear proliferation, and functional maturation of virus-specific CD4+ T cells.

The early events regulating antiviral CD4 responses were tracked using an adoptive transfer model. CD4+ T cell expansion was nonlinear, with a lengthy lag phase followed by 2 days of explosive proliferation. A small number of naive Ag-specific CD4+ T cells were found in nonlymphoid tissues and, in the 8 days following infection, the number of activated cells increased in all tissues analyzed, and their effector functions matured. Finally, we show that a naive mouse contains approximately 100 naive CD4+ precursor cells specific for a single epitope, a precursor frequency of approximately 10(-5), similar to that of naive CD8+ T cells, indicating that the approximately 50-fold difference in size of the two responses to virus infection is determined by something other than the number of precursor cells.

Adoptive Transfer↗
PubMed1976

[Interaction of allogeneic lymphocytes and precursor cells during the primary and secondary immune response].

A mixture of lymph node cells from CBA mice and spleen cells from C57Bl/6J mice stimulated by the cheep erythrocytes fro the first or second time was transplanted in the lethally irradiated mice (CBA X C57Bl/6j)Fl. The interaction of allogenic cells during the secondary immune response was accompanied by the complete inactivation of antibody producents. Under the ratio of interacting cell elements 1 : 1-1 : 2, 93-96% of precursor cells and 98% of antibody forming cells were inactivated. Under the ratio 1 : 5, the index of inactivation of precursor cells fell down to 35%. During the primary response, under the ratio 1 : 1, only 20-48% of precursor cells and 68% of antibody forming cells were inactivated. Under the ratio 1 : 2, no inactivation of precursor cells was observed and, under the ratio 1 : 10, the antibody formation was stimulated. Following the delayed by 1-3 days transplantation of CBA lymphocytes, the cooperative effect was registered with respect to the spleen cells from C57Bl/6J mice stimulated by the erythrocytes for the first time. The interaction of allogenic cells resulted in the 3-4-fold increase in the number of antibody forming cells.

Animals↗
PubMed1999

Insulin in oral immune "tolerance": a one-amino acid change in the B chain makes the difference.

Oral administration of self-Ags can dampen or prevent autoimmune processes by induction of bystander suppression. Based on encouraging results from experiments in nonobese diabetic (NOD) mice, clinical trials have been initiated in type 1 diabetes using human insulin as an oral Ag. However, neither the precise antigenic requirements nor the mechanism of bystander suppression are currently understood in detail. Here we report that 1) a 1-aa difference in position 30 of the insulin B chain abrogated the ability of insulin to confer protection in both NOD as well as a virus-induced transgenic mouse model for type 1 diabetes. In the latter model transgenic mice express the nucleoprotein (NP) of lymphocytic choriomeningitis virus (LCMV) under the control of the rat insulin promotor (RIP) in the pancreatic beta cells and develop diabetes only following LCMV infection; and 2) protection could be transferred with insulin B chain-restimulated but not LCMV-restimulated splenocytes from RIP-NP transgenic mice, demonstrating that the mechanism of diabetes prevention in the RIP-NP model is mediated by insulin B chain-specific, IL-4-producing regulatory cells acting as bystander suppressors.

Administration, Oral↗
PubMed1999

[The role of autologous hematopoietic cell transplantation in adult acute myelogenous leukemia].

High dose chemotherapy with autologous hemopoietic cell transplantation (AHCT) is a common method of treatment of acute myelogenous leukemia (AML). AHCT is a treatment of choice for patients who have no matched family donor. AHCT is particularly recommended for older patients, excluded from allogeneic transplantation procedures. Prospective randomised trials have shown better efficacy of AHCT comparing with conventional chemotherapy in postremission treatment of AML. Both in vitro and in vivo bone marrow purging allow to achieve better transplantation results. Since two years peripheral blood instead of bone marrow is increasingly used as a source of transplant material. It allows more rapid hemopoiesis regrowth. Various methods of immunotherapy such as interleukin-2, Linomid and mixed hemopoietic cell transplantation (delayed donor lymphocytes transfusion) are used to evoke an autologous graft versus leukemia (GvL) phenomenon and to reduce AML relapse rate. Analysis of prognostic factors allows to identify a group of AML patients for whom AHCT is strongly recommended.

Adult↗
PubMed1999

Cell therapy: achievements and perspectives.

BACKGROUND AND OBJECTIVE: Cell therapy can be considered as a strategy aimed at replacing, repairing, or enhancing the biological function of a damaged tissue or system by means of autologous or allogeneic cells. There have been major advances in this field in the last few years. This has prompted the Working Group on Hematopoietic Cells to examine the current utilization of this therapy in clinical hematology. EVIDENCE AND INFORMATION SOURCES: The method employed for preparing this review was that of informal consensus development. Members of the Working Group met three times, and the participants at these meetings examined a list of problems previously prepared by the chairman. They discussed the single points in order to reach an agreement on different opinions and eventually approved the final manuscript. Some of the authors of the present review have been working in the field of cell therapy and have contributed original papers in peer-reviewed journals. In addition, the material examined in the present review includes articles and abstracts published in journals covered by the Science Citation Index and Medline. STATE OF THE ART: Lymphokine-activated killer (LAK) and tumor-infiltrating lymphocytes (TIL) have been used since the '70s mainly in end-stage patients with solid tumors, but the clinical benefits of these treatments has not been clearly documented. TIL are more specific and potent cytotoxic effectors than LAK, but only in few patients (mainly in those with solid tumors such as melanoma and glioblastoma) can their clinical use be considered potentially useful. Adoptive immunotherapy with donor lymphocyte infusions has proved to be effective, particularly in patients with chronic myeloid leukemia, in restoring a state of hematologic remission after leukemia relapse occurring following an allograft. The infusion of donor T-cells can also have a role in the treatment of patients with Epstein-Barr virus (EBV)-induced post-transplant lymphoproliferative disorders. However, in this regard, generation and infusion of donor-derived, virus specific T-cell lines or clones represents a more sophisticated and safer approach for treatment of viral complications occurring in immunocompromised patients. Whereas too few clinical trials have been performed so far to draw any firm conclusion, based on animal studies dendritic cell-based immunotherapy holds promises of exerting an effective anti-tumor activity. Despite leukemic cells not being immunogenic, induction on their surface of co-stimulatory molecules or generation of leukemic dendritic cells may induce antileukemic cytotoxic T-cell responses. Tumor cells express a variety of antigens and can be genetically manipulated to become immunogenic. The main in vitro and in vivo functional characteristics of marrow mesenchymal stem cells (MSCs) with particular emphasis on their hematopoietic regulatory role are reviewed. In addition, prerequisites for clinical applications using culture-expanded mesenchymal cells are discussed PERSPECTIVES: The opportuneness of using LAK cells or activated natural killer (NK) cells in hematologic patients with low tumor burden (e.g. after stem cell transplantation) should be further explored. Moreover the role of new cytokines in enhancing the antineoplastic activity of NK cells and the infusion of selected NK in alternative to CTL for graft versus leukemia (GVL) disease (avoiding graft versus host disease (GvHD) seems very promising. Separation of GVL from GvHD through generation and infusion of leukemia-specific T-cell clones or lines is one of the most intriguing and promising fields of investigations for the future. Likewise, strategies devised to improve immune-reconstitution and restore specific anti-infectious functions through either induction of unresponsiveness to recipient alloantigens or removal of alloreactive donor T-cells might increase the applicability and success of hematopoietic stem cell transplantation. (ABSTRACT TRUNCATED)

Animals↗
PubMed1999

Investigation of the mechanism of lymphocyte injection therapy in treatment of lymphedema with special emphasis on cell adhesion molecule (L-selectin).

We previously employed intraarterial lymphocyte injection therapy in conjunction with standard non-operative treatment of peripheral lymphedema of various etiologies. In this study, we further evaluated the clinical outcome of this therapy in 46 patients with unilateral lymphedema of the extremities. The results showed combined therapy (lymphocyte injection with compression) was effective in 74% (34 of 46 patients) with dramatic reduction in lymphedema in 37% (17 of 46 patients). In the most recent 5 patients treated, we examined the expression of cell adhesion molecule of the lymphocytes (L-selectin) before, during and after lymphocyte injection therapy to study the putative pathomechanism of this treatment method. The expression of L-selectin, a lymphocyte-specific adhesion molecule, increased in the autologous lymphocytes obtained by a blood cell separator and in the lymphocytes from the peripheral blood after injection. Moreover, the lymphocyte fraction, which was positive for L-selectin and negative for CD3, a T-cell marker, decreased after lymphocyte injection. We postulate that the lymphocytes of L-selectin (+) and CD (-) remain in the affected swollen limb and play a role in an ill-defined immunologic responsiveness that potentiates reduction in edema.

Adult↗
PubMed2000

Adoptive immunotherapy in canine mixed chimeras after nonmyeloablative hematopoietic cell transplantation.

Development of nontoxic and nonmyeloablative regimens for allogeneic hematopoietic stem-cell transplantation will decrease transplantation-related mortality caused by regimen-related toxic effects. In pursuit of this goal, a dog model of stable mixed hematopoietic chimerism was established in which leukocyte-antigen-identical litter mates are given sublethal total-body irradiation (2 Gy) before stem-cell transplantation and immunosuppression with mycophenolate mofetil and cyclosporine afterward. In the current study, we examined whether donor lymphocyte infusion (DLI) could be used as adoptive immunotherapy to convert mixed to complete donor chimerism. First, 8 mixed chimeras were given unmodified DLI between day 36 and day 414 after stem-cell transplantation. After a 10- to 47-week follow-up period, there were no significant changes in the percentage of donor engraftment. Next, we immunized the donor to the minor histocompatibility antigens (mHA) of the recipient by means of repeated skin grafting. Lymphocytes from the mHA-sensitized donor were infused between day 201 and day 651 after transplantation. All 8 recipients of mHA-sensitized DLI had conversion to greater than 98% donor chimerism within 2 to 12 weeks of the infusion. Complications from mHA-sensitized DLI included graft-versus-host disease in 2 dogs and marrow aplasia in 1. These results showed that the low-dose transplant regimen establishes immune tolerance, and mHA-sensitized DLI is required to break tolerance, thereby converting mixed to complete donor chimerism. We propose that mixed chimerism established after nonmyeloablative allogeneic stem-cell transplantation provides a platform for adoptive immunotherapy that has clinical potential in the treatment of patients with malignant diseases.

Animals↗
PubMed1979

Immune response to glutaraldehyde-treated cells. I. Dissociation of immunological memory and antibody production.

Glutaraldehyde (GA)-treated sheep red blood cells (SRBC) or H-2-allogeneic spleen cells (SC), induced immunological memory with absent or markedly reduced primary antibody production. In contrast, a normal secondary response was obtained when GA-SRBC or GA-SC were given to mice primed with the corresponding untreated antigens. The secondary response of mice primed and boosted with GA-treated cells was relatively high with GA-SRBC, and negative or very low with GA-SC. Morphological studies of the fate of intraperitoneally injected cells showed that endocytosed GA-SRBC persisted much longer in peritoneal macrophages than untreated SRBC. Simultaneous challenge of mice with untreated and GA-treated SRBC revealed that phagocytosis and digestion of both types of cells in the same macrophage proceeded independently of each other. The primary response of mice receiving both SRBC and GA-SRBC was entirely similar to the response when SRBC alone was given.

Aldehydes↗
PubMed1979

Genetic determination of the immune response in mice to cells of different histological type.

The intensity of the cellular immune response to strong transplantation antigens of the H-2 complex is related to the histological type of cells taken for immunization. Splenic cells from C3H mice immunized BALB/c mice better than cells of non-lymphoid origin from the same donor. The reverse was observed when, instead of BALB/c mice, C57B1/6 and A/He were used in immunization experiments. Analysis of the inheritance of this immunization pattern studied in mice of the first generation from various crosses between strains (BALB/c, C57B1/6 and A/He) and in mice from backcrosses has demonstrated that this immunization pattern is not inherited as a simple Mendelian character. Therefore, it could be supposed that efficiency of immunological control of cells having different histological types, may be genetically determined.

Animals↗
PubMed1975

Differential IgA repopulation after transfer of autologous and allogeneic rabbit Peyer's patch cells.

The distribution and differentiation of rabbit Peyer's patch cells were studied in lethally x-irradiated autologou, and allogeneic recipients, 6 days after i.v. transfer. Immunoglobulin Ig-containing cells were detected in both frozen tissue sections and fixed smears of single cell suspensions of spleens using monospecific anti-alpha, -mu, and -iota antisera in direct immunofluorescence. The tissues of lethally x-irradiated rabbits which had not received any cells were almost devoid of Ig-containing cells whereas the intestinal lamina propria of both autologous and allogeneic Peyer's patch cell recipients had approximately equal numbers of predominantly IgA-containing cells. In the spleen of allogeneic recipients, many large colonies of IgA-containing cells were seen and these cells made up 4.6 to 16.9% (mean 8%) of all spleen cell suspension. The spleens of autologous recipients contained fewer and smaller colonies of IgA cells which made up only 0.5% of all cells in spleen cell suspensions. The numbers of IgM- and IgG-containing spleen cells were small in all animals, however, recipients of allogeneic Peyer's patch cells had four to five times as many as either non-reconstituted lethally irradiated rabbits or autologous recipients. These data confirm that rabbit Peyer's patches are relatively rich in precursors of IgA-producing cells and suggest that histocompatibility differences may either potentiate differentiation of IgA production or lead to trapping of allogeneic Peyer's patch cells in the spleen. Although these experiments did not elucidate the mechanisms of differentiation of IgA-producing cells, the fact that no differences were seen between numbers of IgA cells in gut lamina propria after either autologous or allogeneic cell transfer suggest that different mechanisms may be responsible for appearance of these cells in gut and spleen.

Animals↗
PubMed1975

Immune mechanisms in leukemia: evaluation of immunocompetent cell populations.

Dose-response curves of the cellular immune response of C58/wm mice to syngeneic line Ib malignant lymphoid cells (Ib cells) were computer analyzed by the PROBT subroutine in the IBM Scientific Subroutine Package. An analysis of the relative immunogenicity of various admixtures of x-irradiated (XIb) and viable Ib cells (VIb) after i.p. injection showed that the ratio had to be approximately 100:1 to be immunogenic. Viable Ib cells contained in immunogenic mixtures multiplied in vivo at a logarithmic rate up to 5 or 6 days but were eliminated immunologically by 8 or 9 days. Adoptive cell transfer techniques were used to quantify the protective effect of immune spleen cells (ISC). Essentially a constant dose of ISC (10-6.4) protected mice against a challenge dose of 10-2 to 10-5 VIb cells; more than 10-5 VIb cells were lethal. Two techniques were used to quantify immunity even though mice ultimately died of transplanted leukemia, viz., mean survival time (MST) with a fixed challenge dose of VI b cells, or MST with a fixed time for death. The sensitivity and statistical limitations of these assays are presented. To amplify the sensitivity of assays for adoptive cellular immunity a technique of antigenic stimulation was used, viz., 1 day after x-irradiated mice (600 R) received an i.p. injection of normal or immune spleen, bone marrow or thymic cells they received an i.p. injection of XIb cells containing an admixture of VIb cells. The technique amplified the sensitivity of ISC transfer tests approximately 100-fold and made it possible to detect protective effects of bone marrow and thymic cell populations.

Animals↗
PubMed1976

[Participation of phytohemagglutinin-transformed mouse lymphocytes in development of the "graft-versus-host" reaction].

Transformed lymphocytes obtained as a result of phytohemagglutinin-stimulation of the cells of the lymph nodes of the CBA mice were incapable of realizing the graft-versus-host reaction in administration to the sublethally irradiated (CBAXC57BL/6) F1 hybrids. In this case the graft-versus-host reaction is induced by small untransformed lymphocytes with the same concentration of surface antigens detected by the antilymphocytic serum as in the intact lymphocytes.

Animals↗
PubMed1975

Nippostrongylus brasiliensis in young rats. Lymphocytes expel larval infections but not adult worms.

Young rats were not able to expel adult N. brasiliensis infections even when the worms were damaged by antibodies and the young rats were given all the cellular components (sensitized lymphocytes and bone marrow cells) shown to be necessary for the expulsion of antibody-damaged worms from adult rats. In contrast, most of the worms were expelled from young rats given sensitized lymph node cells on the day of a larval infection. These results show that the reduced ability of young rats to respond to infection by producing sensitized lymphocytes only partly explains their inability to expel the worms. It was not possible to explain the failure of young rats to expel adult worms by hypothesizing that they develop an active factor which prevents the cells from acting on the worms. It is also unlikely that worms persist in young rats because they differ in their susceptibility to cells compared with antibody-damaged worms from mature rats. This work suggests that the immune mechanism which affects the immature stages of this nematode may differ from that which controls the adult stages.

Aging↗
PubMed1975

[Inactivation of hematopoietic stem cells by means of lymphocytes depending upon the genotype of the interacting cells].

Inoculation of a mixture of bone marrow cells with allogeneic lymphocytes into irradiated mice of inbred strains or into F1 hybrids results in the depression of bone marrow cell proliferation in the spleen of the recipient: the effect of inactivation of nonsyngeneic stem cells. The inactivation of stem cells by allogeneic lymphocytes can be detected in all tested combinations of mice strains - donors of lymphocytes and bone marrow cells and mice - recipients but the degree of inactivation differs and depends on the genotype of cell donors rather than on the genotype of the recipient. Lymphocytes of some mice strains (haplotypes H-2k and H-2a) are more active killers of bone marrow cells as compares with lymphocytes of other strains (hyplotypes H-2b and H-2d). Probably, the degree of stem cells inactivation by lymphocytes depends on the differences of their histocompatibility in H-2 system.

Animals↗
PubMedDate not supplied

Fludarabine, cytarabine, G-CSF and idarubicin (FLAG-IDA) for the treatment of relapsed or poor risk childhood acute leukemia.

The prognosis of relapsed acute leukemia or chronic leukemia in acute blast crisis is poor and new chemotherapeutic regimens could be useful for these patients. Six relapsed acute lymphoblastic leukemia (ALL), nine relapsed acute myeloblastic leukemia (AML), one chronic myelomonocytic leukemia (CMML) and one chronic myeloid leukemia (CML) in acute blast crisis between three to 18 years (median 10 years) received fludarabine, cytarabine, G-CSF and idarubicin (FLAG-IDA) chemotherapy (CT). Five of the AML relapses were after bone marrow transplantation (BMT) and four were recurrent relapses. At the end of the second course only three patients (2 AML, 1 ALL) were in complete remission (CR). Of the three patients in CR, one patient with AML had her first donor lymphocyte transfusion (DLT) on the 7th day of the second FLAG-IDA course and she is disease-free on the 30th month of the second remission. The remaining two patients were transplanted from unrelated donors in a BMT center abroad on the 5th and 8th month of the last remission and both died with BMT-related complications. Out of 25 courses, seven resulted in fatal infections. The regimen was ineffective in B-cell ALL as in acute blastic crisis of CMML and CML. We could not evaluate the remission-inducing effect accurately in most of the patients due to induction failure. FLAG-IDA appears to be a myelotoxic therapy for relapsed or poor risk leukemia in a developing country. It is not cost-effective; dose modifications or a regimen without IDA may be tried if there is an available marrow donor.

Adolescent↗