Anti-CD3ε F(ab′)2 Prevents Graft-Versus-Host Disease by Selectively Depleting Donor T Cells Activated by Recipient Alloantigens

Yu, Xue-Zhong; Bidwell, Sasha J.; Martin, Paul J.; Anasetti, Claudio

doi:10.4049/jimmunol.166.9.5835

Cited by 33 publications

(20 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One of the prominent approaches is using nonmitogenic anti-CD3e F(ab') 2 fragments, which effectively confer GVHD protection by partially depleting donor T cells as well as inhibiting their expansion in response to host antigens [23]. Similar to the finding with anti-CD3e F(ab') 2 fragments [24], administration of TAB4 did not cause a complete depletion of alloreactive donor T cells. Nevertheless, after several exposures to TAB4, the number of allogeneic T cells might have fallen below the threshold that is required for developing a lethal GVHD.…”

Section: Discussionsupporting

confidence: 67%

A novel apoptosis-inducing anti-PSGL-1 antibody for T cell-mediated diseases

Huang

Wen

et al. 2005

Eur. J. Immunol.

View full text Add to dashboard Cite

We previously discovered a hamster monoclonal antibody, TAB4, against mouse PSGL-1/CD162 that can induce death of activated T cells. Here, we further investigated the potential of TAB4 in treating two murine models of T cell-mediated diseases. The results showed that administration of TAB4 suppressed incidence and severity of both GVHD and type I diabetes. Analyses of apoptotic T cells ex vivo shortly after antibody injection revealed a higher percentage of apoptosis among activated T cells in the TAB4-treated group than in the control group. Furthermore, restoration of functional donor T cells was observed in TAB4-treated mice. As TAB4 does not affect the binding of P-selectin to activated T cells, our data suggest that its long-lasting therapeutic effect on inhibiting disease progression is attained by specifically inducing apoptosis of activated T cells. These data hence extend our previous finding of the novel property of PSGL-1 and strongly indicate that the PSGL-1-specific apoptosis-inducing antibody is a new therapeutic agent possessing a great potential for controlling GVHD and other T cellmediated autoimmune diseases.

show abstract

Section: Discussionsupporting

confidence: 67%

A novel apoptosis-inducing anti-PSGL-1 antibody for T cell-mediated diseases

Huang

Wen

et al. 2005

Eur. J. Immunol.

View full text Add to dashboard Cite

show abstract

“…For measurement of proliferative responses in vivo, T cells were purified from donor mice and labeled with CFSE (Molecular Probes) as described previously (26). CFSE-labeled cells at 6 -10 ϫ 10 6 /mouse were then transferred via tail vein into previously irradiated allogeneic recipients.…”

Section: Cfse Labeling and Immunofluorescence Analysismentioning

confidence: 99%

Opposing Effects of ICOS on Graft-versus-Host Disease Mediated by CD4 and CD8 T Cells

Liang

Nurieva

et al. 2006

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

ICOS, a CD28 family member expressed on activated CD4+ and CD8+ T cells, plays important roles in T cell activation and effector function. Here we studied the role of ICOS in graft-vs-host disease (GVHD) mediated by CD4+ or CD8+ T cells in allogeneic bone marrow transplantation. In comparison of wild-type and ICOS-deficient T cells, we found that recipients of ICOS−/− CD4+ T cells exhibited significantly less GVHD morbidity and delayed mortality. ICOS−/− CD4+ T cells had no defect in expansion, but expressed significantly less Fas ligand and produced significantly lower levels of IFN-γ and TNF-α. Thus, ICOS−/− CD4+ T cells were impaired in effector functions that lead to GVHD. In contrast, recipients of ICOS−/− CD8+ T cells exhibited significantly enhanced GVHD morbidity and accelerated mortality. In the absence of ICOS signaling, either using ICOS-deficient donors or ICOS ligand-deficient recipients, the levels of expansion and Tc1 cytokine production of CD8+ T cells were significantly increased. The level of expansion was inversely correlated with the level of apoptosis, suggesting that increased ability of ICOS−/− CD8+ T cells to induce GVHD resulted from the enhanced survival and expansion of those cells. Our findings indicate that ICOS has paradoxical effects on the regulation of alloreactive CD4+ and CD8+ T cells in GVHD.

show abstract

“…Lymphocytes from lymph nodes and spleens or purified CD8 ϩ cells were isolated from responder mice, labeled with CFSE (Molecular Probes, Eugene, OR) as previously described (20), and injected via the tail vein into recipients. Recipient mice were exposed to a total body irradiation, so that donor T cells could be easily visualized after adoptive transfer.…”

Section: Transplantationmentioning

confidence: 99%

CD28 Signal Enhances Apoptosis of CD8 T Cells After Strong TCR Ligation

Martin

Anasetti

2003

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

High avidity ligation of the TCR induces negative selection in the thymus and can also induce apoptosis of peripheral T cells. Costimulation through CD28 enhances T cell activation and facilitates negative selection in the thymus, but the role of CD28 in peripheral T cell deletional tolerance has not been investigated. We used 2C CD28 wild-type and 2C CD28-deficient strains to assess the effects of CD28 and TCR avidity on peripheral T cell expansion and apoptosis. We compared the activation, division, expansion, and apoptosis of CD28+/+ and CD28−/− 2C cells in response to self-Ag (Kb), alloantigens with intermediate (Kbm3), high (Ld), or very high (Ld + QL9 peptide) avidity. With intermediate avidity alloantigen, the CD28 signal enhanced T cell activation and expansion. However, when T cells encountered high avidity alloantigen, the CD28 signal reduced T cell expansion and increased apoptosis. These results indicate that the CD28 signal can down-regulate peripheral T cell responses by increasing apoptosis when TCR ligation exceeds a critical threshold.

show abstract

Anti-CD3ε F(ab′)2 Prevents Graft-Versus-Host Disease by Selectively Depleting Donor T Cells Activated by Recipient Alloantigens

Cited by 33 publications

References 18 publications

A novel apoptosis-inducing anti-PSGL-1 antibody for T cell-mediated diseases

A novel apoptosis-inducing anti-PSGL-1 antibody for T cell-mediated diseases

Opposing Effects of ICOS on Graft-versus-Host Disease Mediated by CD4 and CD8 T Cells

CD28 Signal Enhances Apoptosis of CD8 T Cells After Strong TCR Ligation

Contact Info

Product

Resources

About