PATHOLOGIC CHANGES IN OLD NONIRRADIATED F1 HYBRID MICE INJECTED WITH PARENTAL-STRAIN SPLEEN CELLS

The survival of 51Cr-labeled erythrocytes has been studied in F1 hybrid mice in which wasting disease was produced by injection of parental lymphoid cells taken either from lymph nodes and thymus or from the spleen. Coincident with the development of the disease syndrome, there occurred a severe anemia accompanied by a sudden loss of circulating labeled erythrocytes, whether host or parental. This finding suggests that the anemia is not due solely to specific immunologic reaction of donor tissue against host erythrocytes.

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Relative Abilities of Parental Thymus and Spleen Cells to Induce Graft-Versus-Host Reactions and Enhance Antibody Formation in F1 Hybrid Mice

International Archives of Allergy and Immunology ◽

10.1159/000231246 ◽

1974 ◽

Vol 47 (4) ◽

pp. 520-531

Author(s):

L. Lindholm ◽

Ö. Strannegård

Keyword(s):

Antibody Formation ◽

Spleen Cells ◽

F1 Hybrid ◽

Graft Versus Host ◽

Hybrid Mice

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Immunological tolerance in parental strain mice induced by F1 hybrid spleen cells

Transplantation Journal ◽

10.1097/00007890-196609000-00027 ◽

1966 ◽

Vol 4 (5) ◽

pp. 651 ◽

Cited By ~ 5

Author(s):

V. Silobrcic

Keyword(s):

Parental Strain ◽

Immunological Tolerance ◽

Spleen Cells ◽

F1 Hybrid

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IMMUNE MECHANISMS IN PARABIOSIS INTOXICATION

Journal of Experimental Medicine ◽

10.1084/jem.119.4.567 ◽

1964 ◽

Vol 119 (4) ◽

pp. 567-579 ◽

Cited By ~ 8

Author(s):

Henry R. Hilgard ◽

Eugene A. Cornelius ◽

Agustin P. Dalmasso ◽

Carlos Martinez ◽

Robert A. Good

Keyword(s):

Parental Strain ◽

Immunological Tolerance ◽

The Other ◽

Term Survival ◽

F1 Hybrid ◽

Immunological Mechanism ◽

Adult Mice ◽

Hybrid Mice ◽

Normal Hybrid

When A strain mice are placed in parabiotic union with (A x C57Bl/1)F1 hybrid partners, the parental strain partners are polycythemic and the hybrids anemic from the 5th through the 16th parabiosis days. All hybrids develop clinical intoxication between the 7th and the 12th days, and no pairs survive to 1 month. Long-term survival of parabiotic pairs can be achieved if lethally irradiated or specifically tolerant parental strain mice are united to hybrid partners. Production of tolerance by either of these methods results in elimination of anemia-polycythemia by the 12th parabiosis day and prevents intoxication in the hybrid partners. Preimmunization of the parental strain partners against the C57Bl/1 component of the hybrid leads to a considerable intensification of day 5 anemia-polycythemia. Intoxication develops in the hybrid partners between the 4th and the 6th days after union. It is concluded that anemia is primarily responsible for the syndrome of clinical intoxication. Early anemia-polycythemia on day 5 does not depend upon an immunological mechanism, but the late anemia-polycythemia appearing between days 12 and 16 is a function of the ability of the parental strain mouse to react immunologically against its hybrid partner. When neonatally thymectomized A strain mice are joined to hybrid partners, anemia-polycythemia is sustained through the 16th day and the hybrid partners develop clinical intoxication. On the other hand, when both partners are neonatally thymectomized, late anemia-polycythemia is considerably reduced, and the hybrid partners apparently do not develop clinical intoxication. It is concluded that normal hybrid mice are capable of reconstituting the immunological capacity of their thymectomized partners, whereas thymectomized hybrid mice do not have this restorative capacity. These findings are discussed in terms of their possible application to the problem of the induction of immunological tolerance in adult mice by the parabiosis procedure.

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Association of immunity and tolerance to host H-2 determinants in irradiated F1 hybrid mice reconstituted with bone marrow cells from one parental strain.

Journal of Experimental Medicine ◽

10.1084/jem.142.2.321 ◽

1975 ◽

Vol 142 (2) ◽

pp. 321-331 ◽

Cited By ~ 87

Author(s):

J Sprent ◽

H V Boehmer ◽

M Nabholz

Keyword(s):

Bone Marrow ◽

T Cells ◽

Thoracic Duct ◽

Parental Strain ◽

Bone Marrow Cells ◽

Third Party ◽

F1 Hybrid ◽

Host Type ◽

Hybrid Mice ◽

Marrow Cells

Semiallogenetic radiation chimeras were prepared by injecting heavily irradiated F1 hybrid mice with bone marrow cells from one parental strain; the bone marrow cells were treated with anti-theta serum and complement to remove T cells and injected in large numbers (2 times 10-7 cells). The mice survived in excellent health until sacrifice 6 mo later. Thoracic duct cannulation at this stage showed that the mice possessed normal numbers of recirculating lymphocytes. Close to 100% of thoracic duct lymphocytes and lymph node cells were shown to be of donor strain origin. The capacity of lymphocytes from the chimeras to respond to host-type determinants was tested in mixed leukocyte culture and in an assay for cell-mediated lympholysis (CML). Mixed leukocyte reactions (MLR) were measured both in vitro and in vivo; tumor cells and phytohemmaglutinin-stimulated blast cells were used as target cells for measuring CML. While responding normally to third party determinants, cells from the chimeras gave a definite, though reduced MLR when exposed to host-type determinants. However, this proliferative response to host-type determinants, unlike that to third party determinants, was not associated with differentiation into cytotoxic lymphocytes. No evidence could be found that unresponsiveness in this situation was due to blocking serum factors or suppressor T cells. It is argued that the results support the concept that lymphocytes responsive in mixed leukocyte culture have a different specificity to those exerting cell-mediated lympholysis.

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CHRONIC ALLOGENEIC DISEASE

Journal of Experimental Medicine ◽

10.1084/jem.135.3.516 ◽

1972 ◽

Vol 135 (3) ◽

pp. 516-532 ◽

Cited By ~ 35

Author(s):

Helga Gleichmann ◽

Ernst Gleichmann ◽

Janine André-Schwartz ◽

Robert S. Schwartz

Keyword(s):

Fluorescein Isothiocyanate ◽

Spleen Cells ◽

Cell Surface Antigens ◽

Histocompatibility Antigens ◽

F1 Hybrid ◽

Donor Type ◽

Glomerular Lesions ◽

Typical Morphology ◽

Antigen Antibody ◽

Hybrid Mice

The pathogenesis of glomerulonephritis in F1 hybrid mice injected with parental spleen cells was investigated in several ways. Whenever glomerulonephritis developed, the lesion had the typical morphology produced by antigen-antibody complexes. Experiments employing backcross mice demonstrated that the antigen is supplied by the recipient and that it is specified by the H-2 gene complex, or by a locus closely linked to H-2. The source of the antibody was investigated by staining glomerular lesions with fluorescein isothiocyanate-tagged anti-immunoglobulin allotype sera. Only donor-type allotypes could be detected. The ability of the donor's immunocytes to respond to the recipient's histocompatibility antigens in such a way as to produce nephritogenic immune complexes varied from strain to strain, and seemed to be controlled by a gene unrelated to H-2. The results suggest that cell surface antigens, such as histocompatibility antigens, may be of importance in the pathogenesis of several kinds of glomerulonephritis.

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Effect of recent antigen priming on adoptive immune responses. III. Antigen-induced selective recruitment of subsets of recirculating lymphocytes reactive to H-2 determinants.

Journal of Experimental Medicine ◽

10.1084/jem.143.3.585 ◽

1976 ◽

Vol 143 (3) ◽

pp. 585-600 ◽

Cited By ~ 34

Author(s):

J Sprent ◽

J F Miller

Keyword(s):

Parental Strain ◽

Suppressor Cells ◽

Third Party ◽

Spleen Cells ◽

Skin Allograft ◽

Produce Cell ◽

F1 Hybrid ◽

Activated State

Information was sought on the reactivity of thoracic duct lymphocytes (TDL) from parental strain mice injected intravenously with large numbers of irradiated semiallogeneic spleen cells. TDL collected at 1 day after spleen cell injection were almost totally depleted of lymphocytes able to produce cell-mediated lympholysis (CML), a graft-versus-host (GVH) reaction, and skin allograft rejection against the H-2 determinants on the injected spleen cells. Normal or near normal responses were observed against third-party determinants. In the case of CML, there was no evidence that the unresponsiveness was due to suppressor cells. In marked contrast, the capacity of TDL to exert a specific mixed lymphocyte reaction (MLR) against the injected determinants was reduced by no more than two to fourfold; this applied whether MLR were measured in vivo or in vitro. Injection of normal rather than irradiated semiallogeneic spleen cells gave similar results. Complete and specific removal of MLR-producing lymphocytes was achieved, however, in a different system in which parental strain T cells were filtered from blood to lymph through irradiated F1 hybrid mice. Since this system presumably provided a much higher concentration of H-2 determinants to the responding lymphocytes, it is suggested that the differing results obtained with these two systems may indicate that certain cells reactive to H-2 determinants are of low affinity, their reactivity being detected in the MLR, but not by other parameters. With both systems, MLR-producing lymphocytes reappeared in the lymph after 2-3 days; the cells collected at this stage gave an MLR of altered kinetics. The present data, in toto, suggest that under certain conditions of antigen presentation, virtually all recirculating lymphocytes reactive to a given set of H-2 determinants can be induced to leave the circulation for a period of 1-2 days. After responding to the injected determinants (presumably in organs such as the spleen), the cells re-enter the circulation in an activated state after 2-3 days.

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