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

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.

1971 ◽  
Vol 133 (2) ◽  
pp. 169-186 ◽  
Author(s):  
David H. Katz ◽  
William E. Paul ◽  
Edmond A. Goidl ◽  
Baruj Benacerraf

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.


1970 ◽  
Vol 131 (5) ◽  
pp. 936-969 ◽  
Author(s):  
Niels C. Pedersen ◽  
Bede Morris

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.


1969 ◽  
Vol 130 (4) ◽  
pp. 765-775 ◽  
Author(s):  
Nathan Trainin ◽  
Myra Small ◽  
Amiela Globerson

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.


1972 ◽  
Vol 135 (5) ◽  
pp. 1059-1070 ◽  
Author(s):  
Robert E. Tigelaar ◽  
Richard Asofsky

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.


1970 ◽  
Vol 131 (2) ◽  
pp. 223-234 ◽  
Author(s):  
Harvey Cantor ◽  
Richard Asofsky ◽  
Norman Talal

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.


1973 ◽  
Vol 15 (2) ◽  
pp. 215-220 ◽  
Author(s):  
William W. Bonney ◽  
T L Feldbush

1986 ◽  
Vol 72 (6) ◽  
pp. 575-579 ◽  
Author(s):  
Mariano Urdiales-Viedma ◽  
Francisco Nogales-Fernandez ◽  
Sebastian Martos-Padilla ◽  
Emilio Sanchez-Cantalejo

The immnuohistochemical determination of immunoglobulins IgA, IgG and IgM in axillary lymph nodes from 50 unselected breast ductal carcinomas disclosed that lymph nodes with IgG-positive lymphoid follicles and/or metastasized lymph nodes with IgM-positive lymphoid cells are statistically related to breast tumors with a high histologic grade and more than 3 lymph node metastases.


2008 ◽  
Vol 9 (2) ◽  
pp. 96-104 ◽  
Author(s):  
Bent Rolstad ◽  
Sigbjørn Fossum

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