Natural suppressor cells in spleens of irradiated, bone marrow-reconstituted mice and normal bone marrow: Lack of SCA-1 expression and enrichment by depletion of MAC1-positive cells

Sykes, Megan; Sharabi, Yehonatan; Sachs, David H.

doi:10.1016/0008-8749(90)90131-a

Cited by 30 publications

(13 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Two explanations, which are not mutually exclusive, can be brought forward. By week 12, regulatory cells may have developed, which limit GVH reactivity brought about by DLI cells 19,20,23,[25][26][27][28][29][30] or remaining host-type APCs within the lymphohematopoietic compartment in these long-term chimeras may have become so sparse as to preclude the generation of antihost immune responses. Host-derived APCs have indeed been shown to be instrumental in eliciting GVH responses in a murine model of miHC-ag-mismatched BMT.…”

Section: Discussionmentioning

confidence: 99%

“…24 Alternatively or in addition to this, the time interval between transplantation and DLI may allow for development of regulatory cells that keep host-reactive T cells in check. 19,20,23,[25][26][27][28][29][30] Another poorly defined issue is the nature of the GVL effector cells. Because GVHD 31,32 and the use of T cellreplete marrow grafts 31,33 were shown to confer protection against disease relapse, donor T cells can be presumed to be the primary mediators of the GVL response.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Crucial role of timing of donor lymphocyte infusion in generating dissociated graft-versus-host and graft-versus-leukemia responses in mice receiving allogeneic bone marrow transplants

Billiau

Fevery

Rutgeerts

et al. 2002

Blood

View full text Add to dashboard Cite

A murine model of minor histocompatibility antigen-mismatched bone marrow transplantation (BMT) was used to study the role of timing of donor lymphocyte infusion (DLI) in eliciting graft-versushost (GVH) and graft-versus-leukemia (GVL) reactivity. We gave DLI at weeks 3 and 12 after BMT and related its ability to induce a GVL effect with (1) evolution of T cell chimeric status and (2) the extent to which DLI could elicit lymphohematopoietic GVH (LHGVH) reactivity. All mice remained free of GVH disease, but only week 3 DLI chimeras exhibited a significant GVL response when challenged with host-type leukemia cells. In these week 3 DLI chimeras, host-reactive T cells were found to proliferate in vivo (5-[and-6]-carboxyfluorescein diacetate, succinimidyl esther [CFSE]-labeled DLI inocula, TCR-V␤6 ؉ T-cell frequency) and T-cell chimerism rapidly converted from mixed into complete donor type, indicating the occurrence of LHGVH reactivity. In week 12 chimeras, DLI elicited none of the activities noted at week 3. Yet, in both instances, splenocytes, recovered following DLI, generated an equally strong antihost proliferative response in a mixed lymphocyte reaction, thereby arguing against a decisive role of regulatory cells. The lack of in vivo LHGVH reactivity after week 12 DLI was associated with a substantially increased level of pre-existing host-type T-cell chimerism. We conclude that elicitation of a GVL effect may require LHGVH reactivity and that the reason why timing of DLI was critical for obtaining LHGVH reactivity and the desired GVL effect may lie in the evolution of chimeric status. A possible direct involvement of residual host-type antigen-presenting cells in eliciting LHGVH reactivity after DLI should be studied using models that allow chimerism analysis in non-T-cell

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Crucial role of timing of donor lymphocyte infusion in generating dissociated graft-versus-host and graft-versus-leukemia responses in mice receiving allogeneic bone marrow transplants

Billiau

Fevery

Rutgeerts

et al. 2002

Blood

View full text Add to dashboard Cite

show abstract

“…Ϫ CD8 Ϫ Thy1 ϩ T/NK and are known to produce high levels of IL-4 that may affect GVHD responses, experiments in which anti-Thy1 allelic mAb infusion is used to deplete host CD4 ϩ and CD8 ϩ T cells could be difficult to interpret because anti-Thy1 mAb would have effects on other cell populations (17,(31)(32)(33)(34). We do not favor the possibility that anti-Thy1 mAb inhibited DLI-GVH resistance by eliminating an IL-4-producing T/NK cell population for two reasons.…”

Section: Discussionmentioning

confidence: 99%

“…Although these data suggest that either host CD4 ϩ or CD8 ϩ T cells are required for optimal resistance to DLI-GVH, Thy1 is expressed on CD4 Ϫ CD8 Ϫ T/NK cells; therefore, the lower survival observed in anti-Thy1 allelic mAb-treated recipients could be due to resistance mediated by CD4 Ϫ CD8 Ϫ cells (17,(31)(32)(33)(34) T cells have an impaired capacity to expand in vivo in alloantigendisparate recipients, as compared with CD28 ϩ/ϩ T cells (35). To determine whether the absence of CD28 Ag expression on host T cells would interfere with host T cell-mediated DLI-GVHD resistance, CD28…”

Section: The Presence Of Both Host Cd4 ϩ and Cd8 ϩ T Cells And The Comentioning

confidence: 91%

“…Included among the possible explanations as to why DLIs are more well-tolerated include the lower levels of proinflammatory cytokines present as the time from conditioning therapy increases (13), lower numbers of host APCs that are gradually eliminated by conditioning (14), and the existence of regulatory cells (12,(15)(16)(17)(18)(19)(20)(21)(22)(23) that develop later post-BMT and might assist the host in resisting DLI-GVHD. With respect to the latter mechanism, Johnson, Truitt, and colleagues have identified a donor bone marrow (BM)-derived population that suppresses DLI-GVHD (12).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Host T Cells Resist Graft-Versus-Host Disease Mediated by Donor Leukocyte Infusions

Blazar

Lees

Martin

et al. 2000

The Journal of Immunology

View full text Add to dashboard Cite

Delayed lymphocyte infusions (DLIs) are used to treat relapse occurring post bone marrow transplantation (BMT) and to increase the donor chimerism in recipients receiving nonmyeloablative conditioning. As compared with donor lymphocytes given early post-BMT, DLIs are associated with a reduced risk of graft-vs-host disease (GVHD). The mechanism(s) responsible for such resistance have remained incompletely defined. We now have observed that host T cells present 3 wk after lethal total body irradiation, at the time of DLI, contribute to DLI-GVHD resistance. The infusion of donor splenocytes on day 0, a time when host bone marrow (BM)-derived T cells are absent, results in greater expansion than later post-BMT when host and donor BM-derived T cells coexist. Selective depletion of host T cells with anti-Thy1 allelic mAb increased the GVHD risk of DLI, indicating that a Thy1+ host T cell regulated DLI-GVHD lethality. The conditions by which host T cells are required for optimal DLI resistance were determined. Recipients unable to express CD28 or 4-1BB were as susceptible to DLI-GVHD as anti-Thy1 allelic mAb-treated recipients, indicating that CD28 and 4-1BB are critical to DLI-GVHD resistance. Recipients deficient in both perforin and Fas ligand but not individually were highly susceptible to DLI-GVHD. Recipients that cannot produce IFN-γ were more susceptible to DLI-GVHD, whereas those deficient in IL-12 or p55 TNFRI were not. Collectively, these data indicate that host T cells, which are capable of generating antidonor CTL effector cells, are responsible for the impaired ability of DLI to induce GVHD. These same mechanisms may limit the efficacy of DLI in cancer therapy under some conditions.

show abstract

Mechanisms of Tolerance

Sykes¹

2003

Thomas' Hematopoietic Cell Transplantation

View full text Add to dashboard Cite

Natural suppressor cells in spleens of irradiated, bone marrow-reconstituted mice and normal bone marrow: Lack of SCA-1 expression and enrichment by depletion of MAC1-positive cells

Cited by 30 publications

References 32 publications

Crucial role of timing of donor lymphocyte infusion in generating dissociated graft-versus-host and graft-versus-leukemia responses in mice receiving allogeneic bone marrow transplants

Crucial role of timing of donor lymphocyte infusion in generating dissociated graft-versus-host and graft-versus-leukemia responses in mice receiving allogeneic bone marrow transplants

Host T Cells Resist Graft-Versus-Host Disease Mediated by Donor Leukocyte Infusions

Mechanisms of Tolerance

Contact Info

Product

Resources

About