Awareness of Donor Alloantigens in Antiadhesion Therapy Induces Antigen-Specific Unresponsiveness to Islet Allografts1,2

Nishihara, Masayoshi; Gotoh, Mitsukazu; Ohzato, Hiroki; Ohta, Y.; Luo, Zhiyong; Dono, Keizo; Umeshita, Koji; Sakon, Masato; Monden, Morito; Yagita, Hideo; Okumura, Ko; Miyasaka, Masayuki

doi:10.1097/00007890-199710150-00005

Cited by 25 publications

(17 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The Ag-unresponsive T cells have been shown to be a tool for Ag-specific adoptive immunotherapy in transplant medicine (2,3). In this study we observed that adoptive transfer of anti-B7-treated T cells increased fetal viability, whereas adoptive transfer of anti-B7-treated B cells did not.…”

Section: Discussionmentioning

confidence: 47%

“…Thus, induction of maternal immunosuppression to the embryo/fetus is a main concern for maintaining materno-fetal tolerance. In organ transplantation, it has been shown that anergic T cells generated by blocking costimulatory pathway can be transferred as suppresser cells to prevent allograft rejection (2,3). However, to our knowledge, the regulatory role of these T cells treated with anti-B7-1/B7-2 mAbs for suppressing maternal immune responses to the allogeneic fetus in vivo has not been investigated previously.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Adoptive Transfer of Paternal Antigen-Hyporesponsive T Cells Induces Maternal Tolerance to the Allogeneic Fetus in Abortion-Prone Matings

Jin¹,

Li²,

Zhang

et al. 2004

The Journal of Immunology

View full text Add to dashboard Cite

The embryo expresses paternal Ags foreign to the mother and therefore has been viewed as an allograft. It has been shown that anergic T cells generated by blocking of the CD28/B7 costimulatory pathway with anti B7-1 and anti B7-2 mAbs can be transferred as suppresser cells to prevent allograft rejection. Little is known, however, about the in vivo function of anti-B7-treated T cells after their transfer into abortion-prone mice in the maintenance of materno-fetal tolerance. In the present study, abortion-prone CBA/J females mated with DBA/2 males were administered anti-B7-1 and anti-B7-2 mAbs on day 4 of gestation (murine implantation window). The anti-B7-treated T cells subsequently were adoptively transferred into abortion-prone CBA/J mice. We demonstrated that costimulation blockade with anti-B7 mAbs at the time of implantation resulted in altered allogeneic T cell response and overcame increased maternal rejection to the fetus in the CBA/J×DBA/2 system. The transferred anti-B7-treated T cells appeared to be regulatory, decreasing responsiveness and generating clonal deviation in maternal recipient T cells. The transferred CFSE-labeled T cells were found to reside in the spleen and uterine draining lymph nodes, and a few were localized to the materno-fetal interface of the maternal recipient. Our findings suggest that the anti-B7-treated T cells not only function as potent suppresser cells, but also exert an immunoregulatory effect on the maternal recipient T cells, which cosuppresses maternal rejection to the fetus. This procedure might be considered potentially useful for fetal survival when used as an immunotherapy for human recurrent spontaneous abortion.

show abstract

Section: Discussionmentioning

confidence: 47%

mentioning

confidence: 99%

Adoptive Transfer of Paternal Antigen-Hyporesponsive T Cells Induces Maternal Tolerance to the Allogeneic Fetus in Abortion-Prone Matings

Jin¹,

Li²,

Zhang

et al. 2004

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…In the present study, a high systemic production of an immunoadhesin, using Ad-mediated in vivo transfer of the gene encoding sICAM-1/Ig, interfered with the LFA-1-ICAM-1 pathway and significantly prolonged islet allograft survival in mice. Monoclonal antibodies directed against ICAM-1 (Zeng et al, 1994;Katz et al, 2000), LFA-1 (Nishihara et al, 1997;Katz et al, 2000;Nicolls et al, 2000), or both (Grochowiecki et al, 2000;Katz et al, 2000) as well as ICAM-1 antisense oligonucleotides (Katz et al, 2000) have already been used in multiple animal models. According to these data, anti-LFA-1 MAb-specific tolerance has been reported using short-term administration of anti-LFA-1 MAb, confirming the critical role of the LFA-1-ICAM-1 pathway in allograft rejection.…”

Section: Discussionmentioning

confidence: 99%

“…The LFA-1-ICAM-1 interaction plays an essential role in the adhesion of leukocytes to endothelial cells, and is an important costimulatory signal in immunocompetent cells (Springer, 1994). Administration of anti-ICAM-1 and/or anti-LFA-1 monoclonal antibodies (MAbs) has been used in various allo-or xenograft rodent models such as heart (Isobe et al, 1992), islet (Gotoh et al, 1994;Zeng et al, 1994;Nishihara et al, 1997;Katz et al, 2000;Nicolls et al, 2000), small bowel (Sarnacki et al, 2000), pancreas (Kawabe et al, 1996), and liver transplantation (Harihara et al, 1996). Studies of humans confirmed that anti-ICAM-1 or anti-LFA-1 antibodies can significantly prolong kidney or bone marrow graft survival (Fischer et al, 1991;Haug et al, 1993;Hourmant et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

Prolonged Islet Allograft Survival by Adenovirus-Mediated Transfer of sICAM-1/Ig Immunoadhesin Gene

et al. 2002

View full text Add to dashboard Cite

Administration of monoclonal antibodies directed against the leukocyte function-associated antigen 1 (LFA-1)-intercellular adhesion molecule 1 (ICAM-1) pathway showed that these costimulatory molecules play a key role in allograft rejection. Here, adenoviral gene transfer of an immunoadhesin, sICAM-1/Ig, was used to prolong islet allograft survival in a mouse model, and was compared with anti-LFA-1 antibody administration. A replication-deficient recombinant adenoviral vector encoding a chimeric protein, in which the extracellular domain of ICAM-1 is covalently linked to the C(H)2-C(H)3 domains of an IgG1, was used for gene transfer. C3H murine islets were transplanted under the kidney capsule of streptozotocin-induced diabetic BALB/c mice. Experimental groups underwent adenovirus vector administration either in vivo (intravenous injection) or ex vivo (gene transfer to the graft), and control groups received either an empty vector (Ad.null) or an anti-LFA-1 monoclonal antibody. Graft survival was significantly prolonged by in vivo sICAM-1/Ig gene transfer as compared with both Ad.null and anti-LFA-1 groups, but not by ex vivo gene transfer. Histological examination of the grafts showed the presence of a mononuclear infiltrate within functioning grafts, suggesting that the homing of alloreactive T cells was not altered. In vitro T cell proliferation experiments indicated that sICAM-1/Ig exerted agonist effects on both CD4(+) and CD8(+) T cells.

show abstract

“…Isobe et al (5) demonstrated that transient-combined treatment with Abs directed against both LFA-1 and its ligand ICAM-1 triggered profound prolongation and tolerance to cardiac allografts. Other studies since have demonstrated the efficacy of anti-LFA-1 and/or anti-ICAM-1 therapy in experimental and clinical transplantation of islets (6,7), kidney (8,9), bowel (10,11), liver (12,13), bone marrow (14,15), and heart (15)(16)(17).…”

mentioning

confidence: 99%

Anti-LFA-1 Therapy Induces Long-Term Islet Allograft Acceptance in the Absence of IFN-γ or IL-4

Nicolls

Coulombe

Yang

et al. 2000

The Journal of Immunology

View full text Add to dashboard Cite

mAb therapy directed against a variety of cell surface accessory molecules has been effectively utilized to prolong allograft acceptance in various models of tissue and organ transplantation. The purpose of this study was to determine whether transient therapy directed against the adhesion molecule LFA-1 (CD11a) was sufficient to induce donor-specific tolerance to pancreatic islet allografts. Anti-LFA-1 monotherapy was found to be efficacious in inducing long-term islet allograft acceptance in multiple donor-recipient strain combinations. Graft acceptance following anti-LFA-1 therapy was not simply due to clonal ignorance of donor Ags in that the majority of recipients bearing established islet allografts resisted rejection induced by immunization with donor-type APCs. Furthermore, donor-specific tolerance from anti-LFA-1-treated animals could be transferred to secondary immune-deficient animals. Taken together, these results indicated that transient anti-LFA-1 monotherapy resulted in donor-specific tolerance. In vitro, functionally tolerant animals retained normal anti-donor reactivity as assessed by proliferative, cytotoxic, and cytokine release assays that demonstrated that tolerance was not secondary to general clonal deletion or anergy of donor-reactive T cells. Finally, anti-LFA-1 treatment was effective in both IL-4-deficient and IFN-γ-deficient recipients, indicating that neither of these cytokines are universally required for allograft acceptance. These results suggest that anti-adhesion-based therapy can induce a nondeletional form of tolerance that is not overtly dependent on the prototypic Th1 and Th2 cytokines, IFN-γ and IL-4, respectively, in contrast to results in other transplantation models.

show abstract

Awareness of Donor Alloantigens in Antiadhesion Therapy Induces Antigen-Specific Unresponsiveness to Islet Allografts1,2

Abstract: These results indicate that anti-LFA-1 mAb treatment prevents T-cell activation leading to rejection, but results in a T-cell receptor engagement leading to antigen-specific unresponsiveness maintained by transferrable suppressor cells.

Cited by 25 publications

References 16 publications

Adoptive Transfer of Paternal Antigen-Hyporesponsive T Cells Induces Maternal Tolerance to the Allogeneic Fetus in Abortion-Prone Matings

Adoptive Transfer of Paternal Antigen-Hyporesponsive T Cells Induces Maternal Tolerance to the Allogeneic Fetus in Abortion-Prone Matings

Prolonged Islet Allograft Survival by Adenovirus-Mediated Transfer of sICAM-1/Ig Immunoadhesin Gene

Anti-LFA-1 Therapy Induces Long-Term Islet Allograft Acceptance in the Absence of IFN-γ or IL-4

Contact Info

Product

Resources

About