scholarly journals CARRIER FUNCTION IN ANTI-HAPTEN ANTIBODY RESPONSES

1971 ◽  
Vol 133 (2) ◽  
pp. 169-186 ◽  
Author(s):  
David H. Katz ◽  
William E. Paul ◽  
Edmond A. Goidl ◽  
Baruj Benacerraf
Keyword(s):  
Lymph Node ◽  
Guinea Pigs ◽  
Lymphoid Cells ◽  
Antibody Responses ◽  
Host Cells ◽  
Leukemia Cells ◽  
F1 Hybrids ◽  
Spleen Cells ◽  
Graft Versus Host ◽  
Equal Degree

The studies reported here demonstrate that immunocompetent lymphoid cells from allogeneic donor guinea pigs stimulate the synthesis of anti-DNP and anti-OVA antibodies by recipients previously primed with DNP-OVA. This allogeneic effect occurs spontaneously in the absence of any further anti-genic challenge. Furthermore, the transfer of allogeneic cells prepares DNP-OVA-primed recipients for a striking secondary anti-DNP response to DNP-BGG; this occurs in equal degree whether or not the cells are derived from BGG-primed donors. We suggest that the allogeneic cells function by virtue of a specific immunologic attack of grafted cells on host cells. This conclusion is made on the basis of the following evidence: (a) The failure of observing the phenomenon with L2C leukemia cells and irradiated strain 2 lymph node and spleen cells which, although capable of initiating a host-versus-graft response, are incapable of mediating graft-versus-host reactions; and (b) the inability of (strain 2 x strain 13) F1 hybrids to mediate the allogeneic effect in strain 13 recipients. The analysis of this phenomenon may offer a key to the delineation of mechanisms involved in the activation of precursors of antibody-forming cells.

scholarly journals MECHANISM OF GRAFT-VERSUS-HOST-INDUCED LYMPHADENOPATHY IN MICE

1973 ◽  
Vol 137 (5) ◽  
pp. 1293-1302 ◽  
Author(s):  
Eugene E. Emeson ◽  
Donald R. Thursh
Keyword(s):  
Lymph Node ◽  
Lymph Nodes ◽  
Thymidine Incorporation ◽  
Effective Means ◽  
Lymphoid Cells ◽  
Popliteal Lymph Node ◽  
Host Cells ◽  
Immune Reactivity ◽  
Spleen Cells ◽  
Graft Versus Host

Graft-vs.-host (GVH)-induced lymphadenopathy of the popliteal lymph node has been produced in C57BL/6 x A/J F1 (BAF1) mice by injecting A/J spleen cells into the rear footpads. By giving 51Cr-labeled BAF1 lymphoid cells intravenously to the hosts, 24 h before sacrifice, we have demonstrated that a large portion of the GVH-induced lymphadenopathy is due to the trapping of circuating lymphocytes in the challenged lymph nodes. Most of the remaining enlargement can be attributed to proliferation of host cells within the reacting lymph nodes. Conditions have been defined under which the weights and [14C]thymidine incorporation of the popliteal nodes can be plotted against the dose of injected A/J spleen cells on a double-log scale to give a linear dose-response. The popliteal lymph node GVH assay is a simple and effective means of quantitating immune reactivity to histocompatibility antigens in mice.

scholarly journals SYNERGY AMONG LYMPHOID CELLS MEDIATING THE GRAFT-VERSUS-HOST RESPONSE

1972 ◽  
Vol 135 (5) ◽  
pp. 1059-1070 ◽  
Author(s):  
Robert E. Tigelaar ◽  
Richard Asofsky
Keyword(s):  
Lymph Node ◽  
Lymphoid Cells ◽  
Spleen Cells ◽  
Blood Leukocytes ◽  
Graft Versus Host ◽  
Average Survival ◽  
Lymph Node Cells ◽  
The One ◽  
Kinetics Of ◽  
Cell Inoculum

A mortality assay was used to quantitate graft-versus-host (GVH) reactions in sublethally irradiated (400 R) neonatal (C57BL/6 x BALB/c)F1 recipients of BALB/c lymphoid cells from various tissues. The probit of the 35 day cumulative per cent of mortality was a linear function of the logarithm of the cell inoculum for any tissue; reactivities of different tissues fell on a series of parallel lines. Peripheral blood leukocytes (PBL), the most active cells, were about 30 times as active as thymocytes, the least active cells studied; femoral lymph node cells and spleen cells were about 23 and 8 times as reactive as thymocytes, respectively. The average survival time of recipients of thymocytes who eventually died was nearly a week longer than that of recipients of comparably lethal numbers of PBL, lymph node, or spleen cells. Mixtures of PBL and thymocytes gave levels of 35 day mortality significantly greater than those expected if the reactivities of the mixture had been merely the sum of the reactivities of the components measured separately, thereby confirming in any assay independent of host splenomegaly the synergistic interaction of thymocytes and PBL in the GVH reaction. Both populations of cells in the mixture had to be allogeneic to the host in order to observe this synergy. The kinetics of cumulative mortality observed for mixtures of PBL and thymocytes were indistinguishable from those seen with thymocytes alone, indicating activation of the latter cell type. Finally, comparison of the relative abilities of different cell populations to cause splenomegaly on the one hand and lethal runting on the other has raised the possibility that expression of different effector functions of cell-mediated immune reactions may in fact be initiated by distinct cells.

scholarly journals TRANSFER OF RESPONSIVENESS TO HAPTEN CONJUGATES OF POLY-L-LYSINE AND OF A COPOLYMER OF L-GLUTAMIC ACID AND L-LYSINE TO LETHALLY IRRADIATED NON-RESPONDER GUINEA PIGS BY BONE MARROW OR LYMPH NODE AND SPLEEN CELLS FROM RESPONDER GUINEA PIGS

1969 ◽  
Vol 130 (5) ◽  
pp. 1107-1122 ◽  
Author(s):  
John Foerster ◽  
Ira Green ◽  
Jean-Pierre Lamelin ◽  
Baruj Benacerraf
Keyword(s):  
Bone Marrow ◽  
Immune Response ◽  
Lymph Node ◽  
Glutamic Acid ◽  
Graft Versus Host Disease ◽  
Guinea Pigs ◽  
Allogeneic Bone ◽  
Spleen Cells ◽  
Host Disease ◽  
Graft Versus Host

Hartley guinea pigs genetically unresponsive to hapten-PLL (poly-L-lysine) conjugates were lethally irradiated and given allogeneic bone marrow from Hartley responder animals. Many of the animals died of graft versus host disease before their response to 2,4-dinitrophenyl-PLL (DNP-PLL) could be measured. The immune response of the surviving recipient animals was evaluated by anti-DNP antibody production, development of delayed hypersensitivity to DNP-poly-L-lysine, as well as by lymph node cell stimulation in vitro by this antigen. 12 of 14 recipient animals thus treated made an immune response as measured by 2 of the 3 parameters. Strain 13 guinea pigs, genetically unable to respond immunologically to DNP-PLL and to DNP-GL (2,4-dinitrophenyl-L-glutamic acid L-lysine copolymer) were lethally irradiated and given bone marrow from (2 x 13) F1 responder animals or strain 13 bone marrow and (2 x 13) F1 lymph node and spleen cells. A high proportion of the animals survived this procedure; no evidence of graft versus host disease was observed. Three of three strain 13 animals irradiated and, given strain 13 bone marrow and (2 x 13) F1 lymph node and spleen, and then immunized with DNP-PL, made a specific immune response. 7 of 10 irradiated strain 13 animals given strain 13 bone marrow and (2 x 13) F1 lymph node and spleen made an immune response to DNP-GL. However, only one of six irradiated strain 13 animals made a vigorous immune response to DNP-GL after reconstitution with (2 x 13) F1 bone marrow alone. The ability to transfer the immune response to PLL antigens from responder to nonresponder animals demonstrates unequivocally that the defect in the non-responder animals is immunological rather than due to some other type of non-immunological mechanism. The bone marrow contains all the immunological cells necessary for the expression of the PLL gene. However, the finding that (2 x 13) F1 lymph node and spleen cells were more effective than (2 x 13)F1 bone marrow cell populations (known to be a rich source of monocyte precursors) suggests that the cells in which the PLL gene function is expressed may be lymphocytes rather than monocytes and macrophages.

scholarly journals IMMUNOLOGIC INCOMPETENCE OF IMMUNOLOGICALLY RUNTED ANIMALS

1964 ◽  
Vol 119 (2) ◽  
pp. 211-224 ◽  
Author(s):  
R. Michael Blaese ◽  
Carlos Martinez ◽  
Robert A. Good
Keyword(s):  
Parent Strain ◽  
Neonatal Period ◽  
Lymphoid Cells ◽  
F1 Hybrids ◽  
Graft Versus Host Reaction ◽  
Spleen Cells ◽  
Host Reaction ◽  
Graft Versus Host ◽  
Donor Cells ◽  
C3h Mice

1. Adult (A x C57Bl/1)F1 hybrids regularly show runt disease when injected with adult spleen cells from A strain donors. This also occurs when A strain spleen cells are administered to adult C3H mice made tolerant of A strain tissue in the neonatal period. 2. Mice undergoing the graft versus host reaction fail to form antibodies to an intraperitoneal challenge of T2 bacteriophage. This phenomenon was observed well before any of the other overt signs of runting had occurred. Further, inhibition of antibody production to T2 phage by graft versus host reaction initiated at an interval following antigenic stimulation is demonstrated. 3. The basis for the immunologic incompetence of the host with respect to T2 phage is presumed to be the attack of immunologically competent donor cells on the lymphoid cells of the recipient. 4. The failure of the injected parent strain cells to respond to the antigen used may imply immunologic commitment of these cells.

scholarly journals SYNERGY AMONG LYMPHOID CELLS MEDIATING THE GRAFT-VERSUS-HOST RESPONSE

1970 ◽  
Vol 131 (2) ◽  
pp. 223-234 ◽  
Author(s):  
Harvey Cantor ◽  
Richard Asofsky ◽  
Norman Talal
Keyword(s):  
Host Response ◽  
Lymphoid Cells ◽  
Cell Populations ◽  
Spleen Cells ◽  
Graft Versus Host ◽  
Minimum Number ◽  
Number Of Cells

The ability of spleen cells from young (3 month) and old (1 yr) NZB mice to induce GVH reactions in newborn C57BL/6N mice was compared quantitatively using the Simonsen spleen assay. Young NZB cells were five times more reactive than cells from older mice. The minimum number of cells producing detectable reactions was 2 x 106 for the young and 10 x 106 for the old. Young and old cells combined and injected together produced GVH reactions quantitatively similar to those obtained with inocula composed of young cells alone. Mixtures of two cell populations producing no detectable reactions when injected separately into different recipients (1 x 106 young cells and 4 x 106 old cells) produced reactions approximately equal to those obtained with 5 x 106 young cells. As few as 0.25 x 106 young cells were sufficient to effect a reaction when combined with 4.75 x 106 old unreactive cells. Viability of both cell populations was essential for GVH reactivity. This evidence of synergy in GVH reactions indicates that old NZB spleen cells can be rendered immunologically more reactive in the presence of a normally reactive population.

scholarly journals Brief Report: Graft-Versus-Host Reaction in F1 Hybrid Mice Injected with Pre-Immunized Parental Thymus Cells

Blood ◽  
1964 ◽  
Vol 24 (6) ◽  
pp. 770-774 ◽  
Author(s):  
LUCIANO FIORE-DONATI ◽  
LUIGI CHIECO-BIANCHI ◽  
GIUSEPPE DE BENEDICTIS ◽  
GIUSEPPE TRIDENTE
Keyword(s):  
Lymphoid Cells ◽  
The Other ◽  
F1 Hybrids ◽  
Graft Versus Host Reaction ◽  
Host Reaction ◽  
F1 Hybrid ◽  
Graft Versus Host ◽  
Immunologic Activity ◽  
Thymus Cells ◽  
Hybrid Mice

Abstract Dissociated thymus cells are capable of initiating graft-versus-host reaction in (C3Hf/Gs x DBA/2)F1 hybrids only when derived from parental donors previously sensitized against the antigens of the other parental strain. The lower immunologic activity of thymus cells as compared with other lymphoid cells is presumably due to quantitative rather than qualitative differences in immunologically competent cells.

scholarly journals THE ROLE OF THE LYMPHATIC SYSTEM IN THE REJECTION OF HOMOGRAFTS: A STUDY OF LYMPH FROM RENAL TRANSPLANTS

1970 ◽  
Vol 131 (5) ◽  
pp. 936-969 ◽  
Author(s):  
Niels C. Pedersen ◽  
Bede Morris
Keyword(s):  
Lymph Node ◽  
Lymph Nodes ◽  
The Body ◽  
Lymphoid Cells ◽  
Host Cells ◽  
Kidney Graft ◽  
Blood Capillaries ◽  
Renal Lymph ◽  
Peritubular Capillaries ◽  
Blast Cells

The rejection of renal homografts has been studied in sheep by transplanting kidneys into the neck and preserving the renal lymphatic drainage intact. Chronic fistulae were established in the transplanted renal lymphatics and lymph collected throughout the life of the graft. The changes that occurred in homografts during the process of rejection were reflected in changes in the lymph. Large numbers of basophilic, blast, lymphoid cells appeared in the lymph, and lymph production in the grafted kidney increased 20–50 fold. Over a period of about 10 days, up to 60 g wet weight of lymphoid cells and up to 10 liters of lymph were collected from the graft. Within 24 hr of grafting, the host cells present in the renal lymph had become sensitized to the graft and transformed into blast cells when cultivated in Millipore chambers in vitro. When the cells leaving the graft during the first 18–48 hr were injected into distant nonstimulated lymph nodes of the host sheep, they evoked significant cellular and antibody responses in the nodes. Within the graft, the main pathological changes were found in the vascular endothelium and many of the peritubular capillaries become plugged with emboli comprised of blast cells. There was extensive infiltration of the renal parenchyma with lymphoid cells and evidence of their transformation and proliferation within the renal blood capillaries. When all the lymph and cells leaving the homograft were diverted from the body, there was a greatly decreased reaction in the regional prescapular lymph node, and no reaction in lymph nodes distant from the graft. In these circumstances, the survival of the graft was not prolonged, and it was rejected without involvement of the lymph nodes of the host. Humoral antibody was produced in the lymph node regional to the homograft within 48–60 hr of grafting. Antibody was not detected in the blood or in the renal lymph until near to the time the graft was rejected. It was thought that this was due to the binding of antibody by the kidney graft tissue. We conclude that all the events which lead to the recognition and rejection of renal homografts can occur centrally within the graft itself.

scholarly journals IMMUNOCOMPETENCE OF SPLEEN CELLS FROM NEONATALLY THYMECTOMIZED MICE CONFERRED IN VITRO BY A SYNGENEIC THYMUS EXTRACT

1969 ◽  
Vol 130 (4) ◽  
pp. 765-775 ◽  
Author(s):  
Nathan Trainin ◽  
Myra Small ◽  
Amiela Globerson
Keyword(s):  
Host Response ◽  
Protein Concentration ◽  
Lymphoid Cells ◽  
Immune Reactivity ◽  
Spleen Cells ◽  
Graft Versus Host ◽  
Thymus Extract ◽  
Adult Mice ◽  
Thymectomized Mice

Impaired immunological competence of spleen cells from neonatally thymectomized C57B1/6 young adult mice was apparent when these cells were tested in an in vitro graft-versus-host assay. Spleen cell inocula prepared from thymectomized mice did not induce enlargement of (C3H/eb x C57BI/6)F1 newborn spleen explants, whereas the same number of cells from intact donors consistently initiated splenomegaly. Spleen enlargement was observed, however, when the explants were challenged by cells from thymectomized donors in the presence of syngeneic thymus extract, indicating that the spleen cells in suspension attained immunological competence under the influence of a non-cellular component of the thymus. Immunocompetence was also evident when the cells from thymectomized donors were first incubated with thymus extract for 1 hr and subsequently tested for reactivity. Cells from the same thymectomized donor mice exposed in parallel to extracts from syngeneic spleen or mesenteric lymph node at an equivalent protein concentration did not initiate a graft-versus-host response. These experiments demonstrate that immune reactivity in the graft-versus-host response involves activation of lymphoid cells by a humoral factor of the thymus acting directly upon these cells.

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