scholarly journals CELL TO CELL INTERACTION IN THE IMMUNE RESPONSE

1968 ◽  
Vol 128 (4) ◽  
pp. 839-853 ◽  
Author(s):  
G. J. V. Nossal ◽  
A. Cunningham ◽  
G. F. Mitchell ◽  
J. F. A. P. Miller
Keyword(s):  
Bone Marrow ◽  
Immune Response ◽  
Immune Responses ◽  
Thoracic Duct ◽  
Bone Marrow Cells ◽  
Cell Interaction ◽  
Thoracic Duct Lymph ◽  
Chromosomal Marker ◽  
Sheep Erythrocytes ◽  
Marrow Cells

Two new methods are described for making chromosomal spreads of single antibody-forming cells. The first depends on the controlled rupture of cells in small microdroplets through the use of a mild detergent and application of a mechanical stress on the cell. The second is a microadaptation of the conventional Ford technique. Both methods have a success rate of over 50%, though the quality of chromosomal spreads obtained is generally not as good as with conventional methods. These techniques have been applied to an analysis of cell to cell interaction in adoptive immune responses, using the full syngeneic transfer system provided by the use of CBA and CBA/T6T6 donor-recipient combinations. When neonatally thymectomized mice were restored to adequate immune responsiveness to sheep erythrocytes by injections of either thymus cells or thoracic duct lymphocytes, it was shown that all the actual dividing antibody-forming cells were not of donor but of host origin. When lethally irradiated mice were injected with chromosomally marked but syngeneic mixtures of thymus and bone marrow cells, a rather feeble adoptive immune response ensued; all the antibody-forming cells identified were of bone marrow origin. When mixtures of bone marrow cells and thoracic duct lymphocytes were used, immune restoration was much more effective, and over three-quarters of the antibody-forming mitotic figures carried the bone marrow donor chromosomal marker. The results were deemed to be consistent with the conclusions derived in the previous paper of this series, namely that thymus contains some, but a small number only of antigen-reactive cells (ARC), bone marrow contains antibody-forming cell precursors (AFCP) but no ARC, and thoracic duct lymph contains both ARC and AFCP with a probable predominance of the former. A vigorous immune response to sheep erythrocytes probably requires a collaboration between the two cell lineages, involving proliferation first of the ARC and then of the AFCP. The results stressed that the use of large numbers of pure thoracic duct lymphocytes in adoptive transfer work could lead to good adoptive immune responses, but that such results should not be construed as evidence against cell collaboration hypotheses. Some possible further uses of single cell chromosome techniques were briefly discussed.

scholarly journals THE LIFE-SPAN AND RECIRCULATION OF MARROW-DERIVED SMALL LYMPHOCYTES FROM THE RAT THORACIC DUCT

1972 ◽  
Vol 135 (2) ◽  
pp. 185-199 ◽  
Author(s):  
Jonathan C. Howard
Keyword(s):  
Bone Marrow ◽  
Life Span ◽  
B Lymphocytes ◽  
Thoracic Duct ◽  
Bone Marrow Cells ◽  
Thoracic Duct Lymph ◽  
Clear Cut ◽  
Duct Lymph ◽  
Order Of Magnitude ◽  
Marrow Cells

These experiments describe the preparation of pure marrow-derived lymphocyte suspensions from the thoracic duct of thymectomized, irradiated rats reconstituted with bone marrow cells. The majority of marrow-derived cells were small lymphocytes morphologically indistinguishable from small lymphocytes in thoracic duct lymph of normal donors. Marrow-derived small lymphocytes (B lymphocytes) were a predominantly long-lived population; the frequency of short-lived B lymphocytes in the thoracic duct was not significantly higher than the frequency of short-lived small lymphocytes in normal lymph. B lymphocytes transferred to normal recipients recirculated from blood to lymph. The first appearance of intravenously injected B lymphocytes in the thoracic duct was delayed relative to lymphocytes from normal donors and there was no clear cut modal recirculation time. Nevertheless their recirculation over a 48 hr period after transfusion was of the same order of magnitude as that of lymphocytes from normal donors.

scholarly journals CELL TO CELL INTERACTION IN THE IMMUNE RESPONSE

1968 ◽  
Vol 128 (4) ◽  
pp. 801-820 ◽  
Author(s):  
J. F. A. P. Miller ◽  
G. F. Mitchell
Keyword(s):  
Thoracic Duct ◽  
Bone Marrow Cells ◽  
Cell Types ◽  
Cell Interaction ◽  
Thoracic Duct Lymph ◽  
Spleen Cells ◽  
Sheep Erythrocytes ◽  
Duct Cells ◽  
Duct Lymph ◽  
Thymectomized Mice

An injection of viable thymus or thoracic duct lymphocytes was absolutely essential to enable a normal or near-normal 19S liemolysin-forming cell response in the spleens of neonatally thymectomized mice challenged with sheep erythrocytes. Syngeneic thymus lymphocytes were as effective as thoracic duct lymphocytes in this system and allogeneic or semiallogeneic cells could also reconstitute their hosts. No significant elevation of the response was achieved by giving either bone marrow cells, irradiated thymus or thoracic duct cells, thymus extracts or yeast. Spleen cells from reconstituted mice were exposed to anti-H2 sera directed against either the donor of the thymus or thoracic duct cells, or against the neonatally thymectomized host. Only isoantisera directed against the host could significantly reduce the number of hemolysin-forming cells present in the spleen cell suspensions. It is concluded that these antibody-forming cells are derived, not from the inoculated thymus or thoracic duct lymphocytes, but from the host. Thoracic duct cells from donors specifically immunologically tolerant of sheep erythrocytes had a markedly reduced restorative capacity in neonatally thymectomized recipients challenged with sheep erythrocytes. These results have suggested that there are cell types, in thymus or thoracic duct lymph, with capacities to react specifically with antigen and to induce the differentiation, to antibody-forming cells, of hemolysin-forming cell precursors derived from a separate cell line present in the neonatally thymectomized hosts.

scholarly journals CELL TO CELL INTERACTION IN THE IMMUNE RESPONSE

1968 ◽  
Vol 128 (4) ◽  
pp. 821-837 ◽  
Author(s):  
G. F. Mitchell ◽  
J. F. A. P. Miller
Keyword(s):  
Bone Marrow ◽  
Synergistic Effect ◽  
Thoracic Duct ◽  
Cell Types ◽  
Cell Interaction ◽  
Thoracic Duct Lymph ◽  
Sheep Erythrocytes ◽  
Duct Cells ◽  
Duct Lymph ◽  
Thymus Cells

The number of discrete hemolytic foci and of hemolysin-forming cells arising in the spleens of heavily irradiated mice given sheep erythrocytes and either syngeneic thymus or bone marrow was not significantly greater than that detected in controls given antigen alone. Thoracic duct cells injected with sheep erythrocytes significantly increased the number of hemolytic foci and 10 million cells gave rise to over 1000 hemolysin-forming cells per spleen. A synergistic effect was observed when syngeneic thoracic duct cells were mixed with syngeneic marrow cells: the number of hemolysin-forming cells produced in this case was far greater than could be accounted for by summating the activities of either cell population given alone. The number of hemolytic foci produced by the mixed population was not however greater than that produced by an equivalent number of thoracic duct cells given without bone marrow. Thymus cells given together with syngeneic bone marrow enabled irradiated mice to produce hemolysin-forming cells but were much less effective than the same number of thoracic duct cells. Likewise syngeneic thymus cells were not as effective as thoracic duct cells in enabling thymectomized irradiated bone marrow-protected hosts to produce hemolysin-forming cells in response to sheep erythrocytes. Irradiated recipients of semiallogeneic thoracic duct cells produced hemolysin-forming cells of donor-type as shown by the use of anti-H2 sera. The identity of the hemolysin-forming cells in the spleens of irradiated mice receiving a mixed inoculum of semiallogeneic thoracic duct cells and syngeneic marrow was not determined because no synergistic effect was obtained in these recipients in contrast to the results in the syngeneic situation. Thymectomized irradiated mice protected with bone marrow for a period of 2 wk and injected with semiallogeneic thoracic duct cells together with sheep erythrocytes did however produce a far greater number of hemolysin-forming cells than irradiated mice receiving the same number of thoracic duct cells without bone marrow. Anti-H2 sera revealed that the antibody-forming cells arising in the spleens of these thymectomized irradiated hosts were derived, not from the injected thoracic duct cells, but from bone marrow. It is concluded that thoracic duct lymph contains a mixture of cell types: some are hemolysin-forming cell precursors and others are antigen-reactive cells which can interact with antigen and initiate the differentiation of hemolysin-forming cell precursors to antibody-forming cells. Bone marrow contains only precursors of hemolysin-forming cells and thymus contains only antigen-reactive cells but in a proportion that is far less than in thoracic duct lymph.

scholarly journals DISTINCT EVENTS IN THE IMMUNE RESPONSE ELICITED BY TRANSFERRED MARROW AND THYMUS CELLS

1969 ◽  
Vol 130 (6) ◽  
pp. 1243-1261 ◽  
Author(s):  
G. M. Shearer ◽  
G. Cudkowicz
Keyword(s):  
Bone Marrow ◽  
Immune Response ◽  
Bone Marrow Cells ◽  
Second Step ◽  
Cell Divisions ◽  
Cellular Events ◽  
Antigen Complex ◽  
Fresh Bone ◽  
Thymus Cells ◽  
Marrow Cells

Marrow cells and thymocytes of unprimed donor mice were transplanted separately into X-irradiated syngeneic hosts, with or without sheep erythrocytes (SRBC). Antigen-dependent changes in number or function of potentially immunocompetent cells were assessed by retransplantation of thymus-derived cells with fresh bone marrow cells and SRBC; of marrow-derived cells with fresh thymocytes and SRBC; and of thymus-derived with marrow-derived cells and SRBC. Plaque-forming cells (PFC) of the direct (IgM) and indirect (IgG) classes were enumerated in spleens of secondary host mice at the time of peak responses. By using this two-step design, it was shown (a) that thymus, but not bone marrow, contained antigen-reactive cells (ARC) capable of initiating the immune response to SRBC (first step), and (b) that the same antigen complex that activated thymic ARC was required for the subsequent interaction between thymus-derived and marrow cells and/or for PFC production (second step). Thymic ARC separated from marrow cells but exposed to SRBC proliferated and generated specific inducer cells. These were the cells that interacted with marrow precursors of PFC to form the elementary units for plaque responses to SRBC, i.e. the class- and specificity-restricted antigen-sensitive units. It was estimated that each ARC generated 80–800 inducer cells in 4 days by way of a minimum of 6–10 cell divisions. On the basis of the available evidence, a simple model was outlined for cellular events in the immune response to SRBC.

Lidocaine depresses splenocyte immune functions following trauma-hemorrhage in mice

2006 ◽  
Vol 291 (5) ◽  
pp. C1049-C1055 ◽  
Author(s):  
Takashi Kawasaki ◽  
Mashkoor A. Choudhry ◽  
Martin G. Schwacha ◽  
Kirby I. Bland ◽  
Irshad H. Chaudry
Keyword(s):  
Bone Marrow ◽  
Cell Proliferation ◽  
Immune Responses ◽  
Cytokine Production ◽  
Bone Marrow Cells ◽  
Marrow Cell ◽  
Sham Operation ◽  
Mapk Activation ◽  
Midline Laparotomy ◽  
Marrow Cells

Traumatic and/or surgical injury as well as hemorrhage induces profound suppression of cellular immunity. Although local anesthetics have been shown to impair immune responses, it remains unclear whether lidocaine affects lymphocyte functions following trauma-hemorrhage (T-H). We hypothesized that lidocaine will potentiate the suppression of lymphocyte functions after T-H. To test this, we randomly assigned male C3H/HeN (6–8 wk) mice to sham operation or T-H. T-H was induced by midline laparotomy and ∼90 min of hemorrhagic shock (blood pressure 35 mmHg), followed by fluid resuscitation (4× shed blood volume in the form of Ringer lactate). Two hours later, the mice were killed and splenocytes and bone marrow cells were isolated. The effects of lidocaine on concanavalin A-stimulated splenocyte proliferation and cytokine production in both sham-operated and T-H mice were assessed. The effects of lidocaine on LPS-stimulated bone marrow cell proliferation and cytokine production were also assessed. The results indicate that T-H suppresses cell proliferation, Th1 cytokine production, and MAPK activation in splenocytes. In contrast, cell proliferation, cytokine production, and MAPK activation in bone marrow cells were significantly higher 2 h after T-H compared with shams. Lidocaine depressed immune responses in splenocytes; however, it had no effect in bone marrow cells in either sham or T-H mice. The enhanced immunosuppressive effects of lidocaine could contribute to the host's enhanced susceptibility to infection following T-H.

scholarly journals Observations on the binding and interaction of radioiodinated colony- stimulating factor with murine bone marrow cells in vivo

Blood ◽  
1982 ◽  
Vol 59 (2) ◽  
pp. 408-420 ◽  
Author(s):  
G Pigoli ◽  
A Waheed ◽  
RK Shadduck
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Marrow Cell ◽  
Cell Interaction ◽  
Peritoneal Macrophages ◽  
Colony Stimulating Factor ◽  
Murine Bone Marrow ◽  
Stimulating Factor ◽  
Marrow Cells

Abstract Radioiodinated L-cell-derived colony-stimulating factor (CSF) was used to characterize the binding reaction to murine bone marrow cells. The major increment in cell-associated radioactivity occurred over 24 hr incubation at 37 degrees C, but virtually no binding was observed at 4 degrees C. The reaction was saturable with approximately 1 ng/ml of purified CSF. Unlabeled CSF prevented the binding, whereas a number of other hormones and proteins did not compete for CSF uptake. Further specificity studies showed virtually no binding to human bone marrow, which is unresponsive to this form of murine CSF. Minimal CSF uptake was noted with murine peritoneal macrophages, but virtually no binding was detected with thymic, lymph node, liver, or kidney cells. The marrow cell interaction with tracer appeared to require a new protein synthesis, as the binding was prevented by cycloheximide or puromycin. Preincubation of marrow cells in medium devoid of CSF increased the degree of binding after 1 hr exposure to the tracer. This suggests that CSF binding sites may be occupied or perhaps decreased in response to ambient levels of CSF in vivo. Approximately 70% of the bound radioactivity was detected in the cytoplasm at 24 hr. This material was partially degraded as judged by a decrease in molecular weight from approximately 62,000 to 2 peaks of approximately 32,000 and approximately 49,000, but 72% of the binding activity was retained. After plateau binding was achieved, greater than 80% of the radioactivity released into the medium was degraded into biologically inactive peptides with molecular weights less than 10,000. These findings suggest that the interaction of CSF with marrow cells is characterized by binding with subsequent internalization and metabolic degradation into portions of the molecule that are devoid of biologic activity.

Soluble factor and cell-cell interaction in cytostasis induced by bone marrow cells

2000 ◽  
Vol 129 (6) ◽  
pp. 559-561 ◽  
Author(s):  
V. V. Senyukov ◽  
V. I. Seledtsov ◽  
O. V. Poveshchenko ◽  
V. Ya. Taraban ◽  
V. A. Kozlov
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Cell Interaction ◽  
Soluble Factor ◽  
Marrow Cells ◽  
Cell Cell

Pathways in the development of liver macrophages: alternative precursors contained in populations of lymphocytes and bone-marrow cells

1968 ◽  
Vol 169 (1016) ◽  
pp. 307-327 ◽  
Keyword(s):  
Bone Marrow ◽  
Thoracic Duct ◽  
Bone Marrow Cells ◽  
Marker Chromosome ◽  
Proliferating Cells ◽  
Liver Macrophages ◽  
Bone Marrow Precursor ◽  
Liver Macrophage ◽  
Donor Cells ◽  
Marrow Cells

The origin of dividing liver macrophages during states of intense reticulo-endothelial stimulation has been studied in mice by means of the T 6 marker chromosome. The cells were isolated for cytological analysis by means of Garvey’s technique of collagenase and trypsin digestion. During the proliferative phase of graft-versus-host ( GVH ) reaction in the strain combination C 57BL → (C57BL x CBA-T6T6)F 1 , practically all liver macrophages in mitosis were of donor karyotype, even when relatively pure suspensions of thoracic duct small lymphocytes were used as the donor cells. Several lines of evidence established that the dividing cells analysed were part of a macrophage response. The isolated cells in mitosis had macrophage characteristics which reflected the cell proliferation examined in histological sections. This proliferation was largely restricted to the liver sinusoids and to cells with phagocytic properties. The same proportion of these cells appeared to be actively phagoctyic before their arrest in metaphase by Colcemid during GVH reaction as was found in normal mice. Furthermore, more than 70% of the liver sinusoidal cells which incorporated 3 H -thymidine were demonstrably phagocytic before and/or after labelling. Liver macrophage proliferation was greatly depressed by splenectomy 24 h after injection of donor cells, although cells of donor karyotype were still predominant. Similar techniques have been applied to syngeneic radiation chimaeras—( CBA x CBA-T6T6 ) F 1 mice ‘repopulated’ with CBA- T6T6 lymphocytes and CBA bone marrow. When Corynebacterium parvum vaccine was applied as a stimulant, two-thirds of dividing liver macrophages were found to be of lymphocyte origin and one-third or less derived from a precursor in bone marrow cells. Using partial hepatectomy to stimulate macrophage proliferation in these chimaeras, however, it was found that the overwhelming majority were derived from the bone-marrow precursor. The phagocytic property of the majority of proliferating cells was established by combined colloid and 3 H-thymidine labelling. It is concluded that liver macrophages derived from either of two different precursors in populations of recirculating lymphocytes and bone marrow cells respectively can proliferate preferentially, according to the nature of the reticulo-endothelial stimulus. Evidence from a variety of sources supports the contention that the bone-marrow precursor cell represents the major source of ‘normal’ macrophages. Whether the precursor amongst thoracic duct cells is identifiable with any previously recognized category of lymphocyte is not yet known. Its utilization has only been detected so far during conditions of intense reticulo-endothelial stimulation.

scholarly journals CONTRIBUTION OF DIFFERENT CELL TYPES TO THE GENETIC CONTROL OF IMMUNE RESPONSES AS A FUNCTION OF THE CHEMICAL NATURE OF THE POLYMERIC SIDE CHAINS (POLY-L-PROLYL AND POLY-DL-ALANYL) OF SYNTHETIC IMMUNOGENS

1972 ◽  
Vol 135 (5) ◽  
pp. 1009-1027 ◽  
Author(s):  
G. M. Shearer ◽  
Edna Mozes ◽  
Michael Sela
Keyword(s):  
Bone Marrow ◽  
Immune Responses ◽  
Genetic Control ◽  
Bone Marrow Cells ◽  
Marrow Cell ◽  
High Responder ◽  
Side Chains ◽  
Low Responder ◽  
Synthetic Polypeptide ◽  
Marrow Cells

Genetic regulation of immunological responsiveness was studied at the cellular level by comparing the limiting dilutions of immunocompetent cells from spleen, thymus, and bone marrow of high and low responders as a function of the poly-L-prolyl and poly-DL-alanyl side chains of two synthetic polypeptide immunogens. The spleens of immunized and unimmunized high responder DBA/1 mice were found to contain respectively, 18- and 7-fold more limiting precursor cells specific for (Phe, G)-A--L than the spleens of SJL low responder donors. These results, using a synthetic polypeptide built on multichain poly-DL-alanine, confirm the findings reported for polypeptides built on multichain poly-L-proline (1, 2), that there is a direct correlation between immune response potential and the relative number of immunocompetent precursors stimulated. Cell cooperation between thymocytes and bone marrow cells was demonstrated for both (T, G)-Pro--L and (Phe, G)-A--L. Limiting dilutions of thymus and bone marrow cells in the presence of an excess amount of the complementary cell type indicated an eightfold lower number of detected (T, G)-Pro--L-specific precursors in DBA/1 (low responder) marrow when compared with SJL (high responder) marrow. No differences were observed in the frequency of relevant high and low responder thymocytes for the (T, G)-Pro--L immunogen. These results are similar to those reported for the (Phe, G)-Pro--L (3). In contrast to the cellular studies reported for the Pro--L series of immunogens, the marrow and thymus cell dilution experiments for (Phe, G)-A--L revealed genetically associated differences in both the marrow and thymus populations of immunocytes from high (DBA/1) and low (SJL) responders. In addition to a fivefold difference in limiting marrow cell precursors (similar to that seen in the Pro--L studies), a striking difference was observed between the helper cell activity of high responder DBA/1 and low responder SJL thymocytes. This difference was indicated by the observation that low responder thymocyte dilutions followed the predictions of the Poisson model, whereas dilutions of high responder thymocytes did not conform to Poisson statistics. Transfers of allogeneic thymus and marrow cell mixtures from DBA/1 and SJL donors confirmed the syngeneic dilution studies showing that the genetic defect of immune responsiveness to (Phe, G)-A--L is expressed at both the thymus and marrow immunocompetent cell level. The parameters presently known for genetic control of immune responses specific for (Phe, G) (Ir-1 gene) and for Pro--L (Ir-3 gene) have been compared. The Ir-1 and Ir-3 genes are not only distinct by genetic linkage tests (to H-2) (5, 6, 9), but they are also seen to be different by cellular studies. Furthermore, expression of low responsiveness within a given cell population was shown to depend on the chemical structure of the whole immunogenic macromolecule.

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