Cellular basis of graft versus host tolerance in chimeras prepared with total lymphoid irradiation.

Gottlieb, Michael; Strober, Samuel; Kaplan, Henry S.

doi:10.1084/jem.152.3.736

Cited by 7 publications

(3 citation statements)

References 8 publications

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“…Spleen cells from both adult mice given TLI (11) and newborn mice (12,13) contain nonspecific suppressor cells of the mixed leukocyte reaction (MLR) before marrow transplantation. Recent evidence suggests that after transplantation of allogeneic or semiallogeneic lymphoid cells, both TLI-treated adult mice (14,15) and newborn mice (16) or rats (17)(18)(19)(20)(21)(22) develop suppressor cells of transplantation immunity which are specific for the tolerizing tissue antigens.…”

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confidence: 99%

Spleen cells from adult mice given total lymphoid irradiation or from newborn mice have similar regulatory effects in the mixed leukocyte reaction. I. Generation of antigen-specific suppressor cells in the mixed leukocyte reaction after the addition of spleen cells from adult mice given total lymphoid irradiation.

Okada¹,

Strober²

1982

The Journal of Experimental Medicine

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We added spleen cells from adult BALB/c mice treated with total lymphoid irradiation (TLI) to the mixed leukocyte reaction (MLR) using a variety of responder and stimulator cells. The spleen cells nonspecifically suppressed the uptake of [3H]-thymidine and the generation of cytolytic cells regardless of the responder-stimulator combination used. We also examined the effect of the spleen cells on the generation of antigen-nonspecific and antigen-specific suppressor cells in the MLR. The experimental results suggest that the spleen cells from TLI-treated mice inhibit the generation of nonspecific suppressor cells, but do not inhibit the generation of antigen-specific suppressor cells. Thus, alloantigenic stimulation of normal responder cells in vitro in the presence of spleen cells from TLI-treated mice generates large numbers of antigen-specific suppressor cells, but few cytolytic cells or nonspecific suppressor cells. Similar nonspecific inhibition of the MLR was observed with neonatal spleen cells. This in vitro system provides a regulatory model for the induction and maintenance of tolerance in vivo, in which adult mice given TLI or neonatal mice accept allogeneic bone marrow transplants without graft-vs.-host disease.

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confidence: 99%

Spleen cells from adult mice given total lymphoid irradiation or from newborn mice have similar regulatory effects in the mixed leukocyte reaction. I. Generation of antigen-specific suppressor cells in the mixed leukocyte reaction after the addition of spleen cells from adult mice given total lymphoid irradiation.

Okada¹,

Strober²

1982

The Journal of Experimental Medicine

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“…We have previously demonstrated that the donor cell tolerance achieved in C57BL/6-BALB/c stable chimeras is specific to host alloantigens. 17,18 BALB/c mice given allogeneic (C57BL/6) bone marrow cells after lymphoid irradiation become stable chimeras with approximately 80% donor-type and 20% host-type cells in the spleen. 17,18 The levels of donor chimerism closely mimicked those in the current study.…”

Section: Discussionmentioning

confidence: 99%

“…17,18 BALB/c mice given allogeneic (C57BL/6) bone marrow cells after lymphoid irradiation become stable chimeras with approximately 80% donor-type and 20% host-type cells in the spleen. 17,18 The levels of donor chimerism closely mimicked those in the current study. Purified donor cells of C57BL/6 origin from the chimeras mediated GVHD in irradiated C3H (third party), but not in irradiated BALB/c (host-strain) mice.…”

Section: Discussionmentioning

confidence: 99%

Alloantigen recognition is critical for CD8 T cell-mediated graft anti-tumor activity against murine BCL1 lymphoma after myeloablative bone marrow transplantation

Pillai

Teo

George

et al. 2007

Bone Marrow Transplant

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Immunosuppression by fractionated total lymphoid irradiation in collagen arthritis

McCune

Buckley

Belli

et al. 1982

Arthritis & Rheumatism

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Treatments with fractionated total lymphoid irradiation (TLI) and cyclophosphamide were evaluated for rats injected with type I1 collagen. Preadministration of TLI and repeated injections of cyclophosphamide suppressed the severity of arthritis and lowered antibody titers to collagen significantly. TLI initiated at the onset of collagen arthritis decreased humoral and cellular responses to collagen but did not affect the severity of arthritis. These data demonstrate that both TLI and cyclophospharnide are immunosuppressive in an experimentally inducible autoimmune disease.The immunosuppression produced in mice by fractionated total lymphoid irradiation (TLI) can pro-A preliminary account of this work was presented at the annual meeting of the American Rheumatism Association at Boston, MA, June 5 , 1981, and was published in abstract form in Arthritis and Rheumatism, 242359, 1981. From long allogeneic skin (1,2) and bone marrow (2-5) engraftment , expedite the development of tolerance to foreign protein antigens (6), decrease the antibody response to a foreign antigen (7), and ameliorate autoimmune disease in the NZB/NZW (8,9) and MRL/1 (10) strains. In rats, TLI has been shown to facilitate the induction of allograft tolerance (1 1,12), to decrease, preferentially, lymphocyte concentrations in the blood, and to partially suppress adjuvant arthritis (13). In view of the prospect of using this technique [which is a recognized therapy for Hodgkin's disease (14,15)] as an alternative to cytotoxic drug therapy (16,17) in the treatment of patients with severe rheumatoid arthritis (18,19), we investigated whether TLI could modify in rats the clinical, radiographic, and immunologic manifestations of an inflammatory polyarthritis induced by immunization with type I1 collagen (20,21). We also compared the efficacy of TLI with that of cyclophosphamide in this model. MATERIALS AND METHODSRats. We used female Sprague-Dawley rats (Charles River Breeding Laboratories, Wilmington, MA) that weighed 100-130 gm.Collagen and immunization. Rats were immunized during ether anesthesia by intradermal injection of the dorsal skin with approximately 0.4 mg of previously prepared (22) native pepsin-modified chick type I1 collagen dissolved in 0.1M acetic acid and emulsified in incomplete Freund's adjuvant (20). In one experiment, immunized rats were boosted with approximately 0.4 mg of dissolved collagen that was injected intraperitoneally (20).Irradiation. Rats were irradiated with a 250-kV Westinghouse x-ray machine operated at 15 mamp at a rate of 40 rads per minute and a source-axis distance of 60 cm. The beam was corrected with 0.5-mm copper and 1 .O-mm alumi- (13), except for these modifications: the anatomic confines of the thymus and spleen were identified by autopsies, and the ports over these organs were slightly enlarged to ensure total inclusion of these tissues. Because of the lateral scatter that occurs when irradiation is delivered in this energy spectrum (23,24), vertical lead shields, 2 mm in thickness, were positioned...

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Cellular basis of graft versus host tolerance in chimeras prepared with total lymphoid irradiation.

Cited by 7 publications

References 8 publications

Alloantigen recognition is critical for CD8 T cell-mediated graft anti-tumor activity against murine BCL1 lymphoma after myeloablative bone marrow transplantation

Immunosuppression by fractionated total lymphoid irradiation in collagen arthritis

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