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 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.

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

1970 ◽  
Vol 131 (2) ◽  
pp. 235-246 ◽  
Author(s):  
Harvey Cantor ◽  
Richard Asofsky
Keyword(s):  
Cell Types ◽  
Lymphoid Cells ◽  
Cell Populations ◽  
Lymphoid Tissues ◽  
Spleen Cells ◽  
F1 Hybrid ◽  
Graft Versus Host ◽  
Adult Mice ◽  
Thymus Cells ◽  
Old Mice

The capacity of cells from different lymphoid tissues obtained from Balb/c mice to produce graft-vs.-host (GVH) reactions was quantitatively determined in C57BL/6N by Balb/c F1 hybrid recipients. Synergistic responses were observed when small numbers of cells from lymphoid tissues that were rich in GVH activity such as spleen and femoral lymph node were combined with weakly reactive thymus cells. Thymus and spleen cells obtained from 1-wk old mice were separately inactive but produced moderate GVH reactions when combined in equal proportions. GVH activity of spleen cells from mice thymectomized at 3 days of age was partially restored by the addition of small numbers of spleen or thymus cells from adult mice. Changes in ratio between the two cell populations markedly affected the degree of synergy. Synergy was not observed when Balb/c cells were combined with Balb/c x C57BL/6N F1 hybrid cells and inoculated into C57BL/6N recipients, but was demonstrated when Balb/c and C57BL/6N cells were combined and inoculated into F1 recipients, indicating that a genetic disposition to mount GVH reactions in both populations is required to produce synergy. The data indicate that at least two cell types are necessary for GVH reactions, and that synergy between cell populations results from favorable adjustments in the ratio between these two cell types.

Increased graft-versus-host response of parental-strain (donor) lymphoid cells in cyclophosphamide-treated F1 recipients

1976 ◽  
Vol 21 (2) ◽  
pp. 250-256 ◽  
Author(s):  
Robert H. Wander ◽  
Robert W. Derlet ◽  
Henry R. Hilgard
Keyword(s):  
Parental Strain ◽  
Host Response ◽  
Lymphoid Cells ◽  
Graft Versus Host

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 STIMULATION OF ANTIBODY PRODUCTION TO THE HAPTEN 2,4-DINITROBENZENE BY AFFINITY LABELED MURINE LYMPHOID CELLS

1974 ◽  
Vol 139 (4) ◽  
pp. 943-956 ◽  
Author(s):  
David A. Lawrence ◽  
William O. Weigle
Keyword(s):  
Immune Response ◽  
B Cells ◽  
Lymphoid Cells ◽  
Cellular Interaction ◽  
Cell Populations ◽  
Cell Contact ◽  
Spleen Cells ◽  
Normal Spleen ◽  
Thymus Cells

The ability of meta-nitrobenzenediazonium fluoborate (m-NBDF)-labeled thymus and spleen (S) cells to transfer immunity to 2,4-dinitrophenyl (DNP) into irradiated syngeneic recipients was investigated. There was a significant increase in the number of anti-DNP plaque-forming cells (PFC) when m-NBDF-labeled thymus cells and normal spleen cells, or normal thymus cells and m-NBDF-labeled spleen cells were transferred, but not when both thymus- and S-cell populations were labeled and injected together into irradiated recipients. The ability of these cell populations to cooperate and enhance the in vivo immune response to DNP is discussed. The T cells seem to be actively involved in the development of this response; they participate beyond the mere role of carrying and presenting antigen to the B cells. It is suggested that cell to cell contact between T and B cells may be an important factor in the elicitation of an immune response. In addition, the cellular interaction is affected by irradiating the thymus cell preparation and the initiating interaction required for antibody synthesis probably occurs within 48 h after injecting the cell populations into the syngeneic irradiated recipients.

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

1972 ◽  
Vol 135 (4) ◽  
pp. 764-779 ◽  
Author(s):  
Harvey Cantor ◽  
Richard Asofsky
Keyword(s):  
Host Response ◽  
Cell Types ◽  
Lymphoid Cells ◽  
Host Responses ◽  
Cell Type ◽  
Effector Cells ◽  
Graft Versus Host ◽  
Cell Pool ◽  
Small Doses

Two types of thymus-derived (T) lymphocytes have been shown to cooperate in the induction of graft-versus-host responses. One cell type is found in highest concentrations in the peripheral blood and lymph node, is extremely sensitive to anti-thymocyte serum (ATS) in vivo, and is probably part of the recirculating lymphoid cell pool (3). The second cell type, found in highest concentrations in the thymus and spleen, is relatively resistant to small doses of ATS in vivo. Both cell types are substantially depleted after neonatal thymectomy. Moreover, since synergism was also obtained using appropriate mixtures of cells from either parental strain in F1 hosts, it was possible to show that the nonrecirculating cells determined the specificity of the response and were probably the precursors of effector cells in this response. The recirculating T cell appeared to amplify this response. The implications of these data are discussed.

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

1973 ◽  
Vol 137 (2) ◽  
pp. 239-253 ◽  
Author(s):  
Robert E. Tigelaar ◽  
Richard Asofsky
Keyword(s):  
Normal Population ◽  
Lymphoid Cells ◽  
Spleen Weight ◽  
Spleen Cells ◽  
Parent Population ◽  
Graft Versus Host ◽  
Adult Mice ◽  
Peripheral Lymph ◽  
Normal Expression

Spleen cells from normal adult mice were injected into lethally irradiated adult syngeneic recipients. 24 h later, cell suspensions were prepared from the recipients' spleens or peripheral lymph nodes and tested either alone or combined for their capacity to elicit graft-versus-host (GVH) reactions in neonatal F1 recipients, using the Simonsen spleen weight assay. Either the lymph node-seeking subpopulation or the spleen-seeking subpopulation alone was markedly deficient in its ability to provide a GVH reaction when compared with the normal population from which it was derived. However, an appropriate mixture of the two had a reactivity characteristic of the parent population. Both subpopulations were sensitive to treatment with anti-θ antibody and complement in vitro. These results provide a convincing demonstration of the functional heterogeneity within the pool of thymus-derived cells present in a single normal lymphoid tissue. They strongly suggest that the normal expression of GVH reactivity of such a tissue involves an interaction among distinct subpopulations of thymus-derived 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 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 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.

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