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Unresponsiveness to human leukocytes in immunosuppressed mice by combined donor-derived human transferrin and antigens.

Abstract：

:Previous work on the facilitation of xenogeneic and allogeneic bone marrow engraftment in irradiated mice and dogs with transferrins allowed the development of a model for induction of an apparently durable state of immunological unresponsiveness or 'tolerance' in chemically immunosuppressed mice. The system is based on the simultaneous and combined administration of donor-derived cell antigens, namely human leukocytes, and specific donor-derived or plasma pool human transferrin into BALB/c or C57BL/6 mice previously treated with prednisolone and cyclophosphamide on day 0 and day 1 of the experiment. A properly timed presentation of both donor-specific or plasma pool transferrin and leukocyte antigens into the mice on day 3 and day 16 of the experiment, in the course of initial restoration of their lymphohaemopoietic tissues and cells after severe immunosuppression, results 1-3 months later, in their inability to 'recognize' human donor lymphocytes and to mount an immediate or a delayed-type immune response against human antigens. This durable state of unresponsiveness was evaluated by a complement-mediated cytotoxicity assay, with a mixed lymphocyte culture method and confirmed by the abrogation of the humoral (antibody response to human erythrocytes) and of the cell-mediated (popliteal lymph node test) immune responses in vivo. Our findings demonstrate the capacity of human plasma-derived transferrins to induce a state of durable unresponsiveness (xenogeneic tolerance?) in mice when administered with human antigens in the course of regeneration of stem cells in the bone marrow and lymphatic organs.

journal_name

Transpl Immunol

journal_title

Transplant immunology

authors

Pierpaoli W,Lesnikov VA,Lesnikova MP,Arrighi S,Bardotti A

doi

10.1016/s0966-3274(96)80051-7

subject

Has Abstract

pub_date

1996-12-01 00:00:00

pages

301-8

issue

4

eissn

0966-3274

issn

1878-5492

pii

S0966-3274(96)80051-7

journal_volume

4

pub_type

杂志文章

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