Further Studies of Veto Activity in Rhesus Monkey Bone Marrow in Relation to Allograft Tolerance and Chimerism

Thomas, Judith M.; Carver, F. Melinda; Kasten‐Jolly, Jane; Haisch, Carl E.; Rebellato, Lorita M.; Gross, U; Vore, Stephen J.; Thomas, Francis T.

doi:10.1097/00007890-199401000-00018

Cited by 121 publications

(33 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[1][2][3][4][5][6]23,[31][32][33][34][35][36] This approach was successfully implemented in the treatment of heavily pretreated patients with leukemia, allowing engraftment of 3-loci-mismatched, CD34 ϩ stem cell transplants from haploidentical family members. [37][38][39] Thus, the residual host immunity previously shown to be associated with a high rate of graft rejection (mediated predominantly by CTL-p [40][41][42] ) in such transplants was overcome by using large doses of CD34 ϩ cells.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Tolerance induction by megadose hematopoietic progenitor cells: expansion of veto cells by short-term culture of purified human CD34+ cells

Gur

Krauthgamer

Berrébi

et al. 2002

Blood

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

“…No inhibition was detected when CD34 ϩ cells were added on day 2 or later. Thus, the veto effect of CD34 ϩ cells, similar to that of other veto cells, [21][22][23][24] acts in the early induction phase of allogeneic CTLs.…”

Section: Inhibition Of Antidonor Response Requires the Addition Of CDmentioning

confidence: 99%

Tolerance induction by megadose hematopoietic progenitor cells: expansion of veto cells by short-term culture of purified human CD34+ cells

Gur

Krauthgamer

Berrébi

et al. 2002

Blood

View full text Add to dashboard Cite

show abstract

“…The PCR-flow assay, combining the sensitivity of DNA amplification techniques with the detection of CD epitopes using monoclonal antibody flow cytometry analysis has now allowed for the detection of several specific cell lineages of donor origin in the recipient. It has the potential of eventually identifying the presence of such "facilitating cells" (35,36) and equating this with immunological unresponsiveness. The in vitro assays described in this report, however, have demonstrated nonspecific rather than donor specific immune inhibitory effects of the donor marrow, i.e., possibly because of nonspecific effects of "suppressor cell" subsets (33,37,38).…”

Section: Discussionmentioning

confidence: 99%

The effects of chimeric cells following donor bone marrow infusions as detected by PCR-flow assays in kidney transplant recipients.

et al. 1997

View full text Add to dashboard Cite

Abstract40 recipients of first cadaver kidney transplants were given perioperative donor vertebral bone marrow infusions (DBMC), compared with 100 controls who did not receive donor bone marrow. The immunosuppressive regimen included OKT3, Tacrolimus, and steroid maintenance therapy, and, in some patients, newly introduced mycophenolate mofetil. This report describes the 24-mo actuarial follow-up and several immunological monitoring studies including sequential measurements of donor bone marrow lineage subset chimerism by the recently reported PCR-flow assay. This is a sensitive in situ PCR detection system for donor versus recipient histocompatibility genes as well as cell surface CD epitope markers using flow cytometry. The results indicate ( a ) the stabilization of the donor CD3 ϩ and CD34 ϩ cells in recipient peripheral blood at levels below 1% between 6 mo and 1 yr postoperatively, with a 10-fold higher level of donor cell chimerism of these lineages in recipient iliac crest marrow; ( b ) significantly lower levels of chimerism in peripheral blood up to 6 mo postoperatively in patients who had early acute (reversible) rejection episodes compared with those who did not; ( c ) a higher degree of chimerism seen in patients who were class II MHC HLA DR identical with their donors; ( d ) the identification of a high proportion of the donor bone marrow derived CD3 dimly staining subset of T cells (to which regulatory functions have been ascribed) in recipient peripheral blood and especially in recipient bone marrow; and ( e ) an unexpectedly increased susceptibility to clinically significant infections (primarily viral), and even death in the DBMC-infused group, compared with controls, but no graft losses because of rejection in the DBMC-infused group. Mixed lymphocyte culture assays showed a trend toward a greater number of nonspecifically low reactors in the DBMC group, as well as a greater number of nonspecifically high reactors in the controls ( P ϭ 0.058). The autologous mixed lymphocyte reaction also indicated a trend towards nonspecific immune activation in the DBMC group. Finally, anti-cytomegaloviral IgG antibody reactivity was significantly inhibited in the DBMC group 4-6 mo postoperatively ( P ϭ Ͻ 0.05). In the controls, there were no donor cell lineages detected by PCR-flow in the peripheral blood. These rather unexpected findings, indicating a more depressed cellular and humoral immune capacity in the DBMC cadaver kidney transplant recipients in this relatively early follow-up period, are discussed relevant to chimerism, MHC restriction, and suppressor activity brought about by specialized DBMC subsets, which still need to be defined. ( J. Clin. Invest. 1997. 99:1118-1129.)

show abstract

“…However, only a few strategies have been successfully translated to nonhuman primate models (1)(2)(3)(4)(5). Heterologous immunologic memory induced by exposure to environmental pathogens in primates, has been suggested as one explanation for this critical discrepancy (6)(7)(8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

Depletion of CD8 Memory T Cells for Induction of Tolerance of a Previously Transplanted Kidney Allograft

Koyama

Nadazdin

Bosković

et al. 2007

American Journal of Transplantation

113

101

View full text Add to dashboard Cite

Heterologous immunologic memory has been considered a potent barrier to tolerance induction in primates. Induction of such tolerance for a previously transplanted organ may be more difficult, because specific memory cells can be induced and activated by a transplanted organ. In the current study, we attempted to induce tolerance to a previously transplanted kidney allograft in nonhuman primates. The conditioning regimen consisted of low dose total body irradiation, thymic irradiation, antithymocyte globulin, and anti-CD154 antibody followed by a brief course of a calcineurin inhibitor. This regimen had been shown to induce mixed chimerism and allograft tolerance when kidney transplantation (KTx) and donor bone marrow transplantation (DBMT) were simultaneously performed. However, the same regimen failed to induce mixed chimerism when delayed DBMT was performed after KTx. We found that significant levels of memory T cells remained after conditioning, despite effective depletion of naïve T cells. By adding humanized anti-CD8 monoclonal antibody (cM-T807), CD8 memory T cells were effectively depleted and these recipients successfully achieved mixed chimerism and tolerance. The current studies provide 'proof of principle' that the mixed chimerism approach can induce renal allograft tolerance, even late after organ transplantation if memory T-cell function is adequately controlled.

show abstract

Further Studies of Veto Activity in Rhesus Monkey Bone Marrow in Relation to Allograft Tolerance and Chimerism

Cited by 121 publications

References 0 publications

Tolerance induction by megadose hematopoietic progenitor cells: expansion of veto cells by short-term culture of purified human CD34+ cells

Tolerance induction by megadose hematopoietic progenitor cells: expansion of veto cells by short-term culture of purified human CD34+ cells

The effects of chimeric cells following donor bone marrow infusions as detected by PCR-flow assays in kidney transplant recipients.

Depletion of CD8 Memory T Cells for Induction of Tolerance of a Previously Transplanted Kidney Allograft

Contact Info

Product

Resources

About