Marrow-dependent Cells Research Articles

Marrow-dependent cells depleted by 89Sr mediate genetic resistance to herpes simplex virus type 1 infection in mice.

Adult mice resistant to infection with 10(6) plaque-forming units of a virulent strain of herpes simplex virus type 1 were treated with 89Sr to abrogate marrow-dependent cell functions. Treated mice were found to be much more susceptible to the herpes simplex virus type 1 infection than untreated mice. The virus persisted in the visceral tissues of 89Sr-treated mice for 3 or more days postinfection but not in those of untreated mice. The virus also spread to the spinal cords of treated but not untreated mice. A marrow-dependent cell appeared to mediate resistance to herpes simplex virus type 1 by controlling the infection early after inoculation and not allowing the infection spread to the central nervous system.

Hybrid resistance to EL-4 lymphoma cells. I. Characterization of natural killer cells that lyse EL-4 cells and their distinction from marrow-dependent natural killer cells.

Natural killer (NK) cells from nonimmunized mice capable of lysing EL-4 (C57BL/6 strain H-2b) tissue culture-adapted lymphoma cells have been analyzed and compared with NK cells which lyse YAC-1 (A-strain, H-2a) lymphoma cells. A correlation was seen in the ability of inbred and B6D2F1 mice to reject C57BL/6 (B6) bone-marrow grafts and the ability of their spleen cells to lyse EL-4 cells in vitro. This suggests that hybrid or hemopoietic histocompatibility antigens, (Hh-1b), relevant in the rejection of B6 stem cells may also be the relevant target structures for the anti-EL-4 NK cells. Certain features of these NK cells are similar to the NK cells reactive against YAC-1 cells. Both types of NK cells are present in athymic nude mice, are not affected by treatment with anti-immunoglobulin plus complement, and are not depleted by techniques that remove macrophages. NK activity against both targets is stimulated 3 d after injection of Corynebacterium parvum, and 24 h after challenge with polyinosinic:polycytidylic acid. Hydrocortisone acetate and cyclophosphamide lead to reduction of NK activity within 2-3 d after administration. However, the anti-YAC and anti-EL-4 NK reactivities differed in several important respects. Treatment of mice with 89Sr, the bone-seeking isotope, to deplete marrow-dependent cells, depleted the anti-YAC-1 but not anti-EL-4 cell functions. Anti-EL-4 NK cells were unaffected by silica particles in vivo or in vitro; the NK cells reactive to EL-4 cells matured functionally much earlier in life (5 d of age) and the function did not decline with age. Irradiated mice reconstituted with syngeneic marrow or spleen cells developed functional NK cells against EL-4 targets before they developed anti-YAC-1 NK cells in their spleen. Thus anti-EL-4 NK cells that express hybrid resistance in vitro appear to differ from anti-YAC-1 NK cells and do not require an intact marrow microenvironment for functional differentiation. Despite differences in the NK-cell types involved in the lysis of YAC-1 and EL-4 cells, these two tumor cells share certain common determinants. This was ascertained both by cold competition and by utilization of YAC-1 and EL-4 cell monolayers as immunoadsorbents. We conclude that Hh-1b is the common antigen present in EL-4 and YAC-1 cells, because B6D2F1 anti-B6 (anti-Hh-1b) cytotoxic T lymphocytes lysed both the tumor cells. Our data suggest that Hh-1b antigen is recognized by both types of NK cells, but that additional determinants must be present on YAC-1 cells. Two models of NK cell lysis compatible with the data are presented.

Spontaneous Regression of Friend Murine Leukemia Virus-Induced Erythroleukemia. IV. Effects of Radiation and Athymia on Leukemia Regression in Mice<xref ref-type="fn" rid="FN2">2</xref>

The spontaneous regression of the erythroleukemia induced by the regressing Friend murine leukemia virus (F-MuLV) complex was inhibited by irradiation of the animals prior to F-MuLV inoculation. This inhibition was proportional to the dose of radiation used. Treatment of the mice with the bone-seeking isotope 89Sr also inhibited erythroleukemia regression, which implicates the same effector mechanisms involved in the resistance to F-MuLV or F-MuLV-induced immunosuprression. Erythroleukemias induced in athymic nude mice by the regressing F-MuLV complex exhibited higher rates of lethality than did the leukemias in heterozygous or homozygous thymus gland-containing controls. These data suggested the involvement of the immune system in erythroleukemia regression and the specific participation of thymus cells and an 89Sr-susceptible function, perhaps marrow-dependent cells, in the process of regression.

Natural Killer Cells, Bone, and the Bone Marrow: Studies in Estrogen-Treated Mice and in Congenitally Osteopetrotic (mi/mi) Mice

Abstract Mice lose natural killer cells after 6 weeks of treatment with 17β-estradiol. We here demonstrate that the same protocol leads to loss of genetic resistance to bone marrow transplantation and to significant osteoproliferation with loss of bone marrow. We also show that mice with reduced marrow because of congenital osteopetrosis are deficient in natural killing. These findings are consistent with previous evidence that natural killing and genetic resistance to bone marrow transplantation are dependent upon the marrow. Temporal studies of bone histology and radiology during and after treatment with estrogen reveal that alterations in natural killing proceed more rapidly than changes in bone marrow volume. These studies also demonstrate that estrogens induce osteoproliferation only at endosteal surfaces that are adjacent to hematopoietic marrow. From these observations, we conclude that estrogens do not reduce natural killer cells simply by reducing the volume of bone marrow. Estrogens may instead have an effect on bone marrow cells that leads both to osteoproliferation and to a deficiency of marrow-dependent cells.

Receptor activity of sorted lymphoid cells with a thymic regulatory factor

A small molecular-weight regulatory factor from the thymus has been shown to enhance both cell-mediated and humoral immune responses. In this study, the relative binding capacity of the factor to thymus-dependent and bone marrow-dependent lymphocytes was measured directly. Spleen cells were separated using an automated, multiparameter, cell sorting instrument. Receptor activity for the iodinated thymic protein of each population was determined. Based on a number of criteria, thymus-dependent cells exhibited a greater affinity for the regulatory protein than did the bone marrow-dependent cells. These results indicate that the mechanism of action of regulatory control is via receptor-ligand interactions of specific subpopulations of lymphoid cells with a humoral factor.

Marrow-dependent cell function in early stages of infection with Listeria monocytogenes

Mice were infected with either Listeria monocytogenes (LM) or Yersinia pestis EV 76 stain ( YP), which are facultative intracellular and extracellular organisms, respectively. Bacterial growth in spleen was determined at various intervals following challenge, focusing particularly on the critical period prior to the emergence of specific immunity. Natural resistance to LM during the first 2 days was diminished by treatment of adult mice with 80Sr or silica particles, but not by treatment with lethal total-body irradiation, cortisol, or cyclophosphamide (CY). Early stages of resistance to YP were unaffected by 80Sr, but were reduced by lethal total-body irradiation, silica particles, cortisol, and (CY). Infant mice manifested no resistance comparable to that of adults against LM prior to 19 days of age, whereas resistance against YP was attained by 14 days of age. The data are consistent with the hypothesis that marrow-dependent (M) cells function in host defense against early stages of infection with LM but not with YP.

Mechanisms of genetic resistance to Friend virus leukemia in mice. II. Resistance of mitogen-responsive lymphocytes mediated by marrow-dependent cells.

Friend leukemia virus suppresses the proliferative responses of normal thymus-dependent (T) and bursa equivalent-dependent (B) lymphocytes from spleen, thymus, lymph node, and bone marrow to mitogens. The suppressive effect of Friend virus complex (FV) requires fully infectious virions. Friend erythroleukemic cells, washed to removed extracellular virus, fail to suppress concanavalin A (Con-A)-induced mitogenesis of normal spleen cells. This indicates that FV does not mediate its immunosuppressive effect via transformed erythropoietic cells. The in vitro suppressive effect of FV on lymphocyte mitogenesis is under host genetic control. Spleen, bone marrow, and thymus cells from strains of mice susceptible to FV-induced leukemogenesis in vivo were quite susceptible to the suppressive effects of FV in vitro. On the other hand, similar cells from strains of mice such as C57BL/6 resistant to Friend erythroleukemia, were quite resistant to in virto immunosuppression by FV. Mitogenesis of splenic T cells from resistant B6 mice, previously treated with 89Sr, became susceptible to suppression by FV. This indicated that the in vitro resistance of lymphocytes to FV-induced suppression is not an intrinsic property of T cells, but is controlled by marrow-dependent (M) cells which are selectively eliminated by treatment with 89Sr. M-cell function does not develop in mice less than 3-wk old. The Con A response by thymus cells from 2-wk-old B6 mice was susceptible to suppression by FV, further supporting the concept that M cells may regulate the genetic resistance to FV.

Discoid lupus erythematosus with macroglobulinemia: Correlations between autoimmunity and B cell malignancy with hyperimmunoglobulinemia

A 44 year old woman presented with discoid lupus erythematosus and then chronic lymphocytic leukemia of the B cell type with macroglobulinemia developed. Immunologic studies revealed suppressed thymus-dependent cell function, increased bone marrow-dependent cells of the immunoglobulin M (IgM) class and increased null cells. The pathogenesis and relation of lupus erythematosus to B cell malignancy with hyperimmunoglobulinemia are discussed.