Mechanisms of rejection during OKT3 therapy: Propagation and characterization of CD3 resistant allospecific cytotoxic T cells from a rejecting liver allograft

Sutherland, Francis; Abou-Jaoudé, Maroun M; White, Martin; Yamada, Jane; Ghent, Cameron N.; Grant, David; Wall, William; García, Bertha; Mazaheri, Reza; Lazarovits, Andrew I.

doi:10.1016/0090-1229(91)90110-v

Cited by 5 publications

(2 citation statements)

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“…Sutherland e t a l. demonstrated a clonal expansion of OKT3-resistant, allospecific T cells within the graft of a patient experiencing rejection during OKT3 induction. 3 These cells maintained IL2 production in vitro despite binding of OKT3. This sustained IL2 production may be important for the escape phenomenon.…”

Section: Discussionmentioning

confidence: 96%

“…2 The central role of IL2 in T cell activation and proliferation is well documented, while IFNg has been shown to stimulate B cells, macrophages and expression of MHC class I and II molecules. 3 Administration of OKT3 results in significant release of proinflammatory cytokines, such as TNFa and IL1b. Circulating levels of the T-cell derived cytokines IFNg and IL2 also rise following OKT3 injection.…”

Section: Introductionmentioning

confidence: 99%

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Cytokine profiles in early rejection following OKT3 treatment in liver transplant patients

Roayaie

Sheiner

Emre

et al. 2000

Mediators of Inflammation

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OKT3 , a murine monoclonal antibody specific to the human CD3 complex, induces immunosuppression by depletion of T cells. Administration of OKT3 results in significant release of proinflammatory cytokines, such as TNFalpha and IL1beta. Liver recipients who experience rejection within 3 weeks after transplantation with OKT3 prophylaxis recover their T cells by postoperative day 10 despite complete initial clearance. We sought to analyze the role of proinflammatory and Th-1 cytokines in T cell recovery and rejection after liver transplantation with OKT3 prophylaxis. In plasma samples from 32 patients, we measured TNFalpha, IL1beta and IL6 (before transplant and on postoperative days 1, 2 and 3) and IL2, IFNgamma, sIL2R and slCAM (postoperative days 5, 7 and 10) and examined possible correlations with T-cell recovery and occurrence of rejection within 3 weeks. TNFalpha, IL1beta, and IL6 did not correlate with T-cell recovery. In patients who rejected, IL2 and IFNgamma on postoperative days 5 and 7 correlated with degree of T-cell recovery by day 10; a significant rise in sIL2R over time also correlated with T-cell recovery in this group. Our results emphasize the role of Th-1 cytokines in rejection following OKT3 induction and suggest that markers of T cell activation may predict risk.

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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Cytokine profiles in early rejection following OKT3 treatment in liver transplant patients

Roayaie

Sheiner

Emre

et al. 2000

Mediators of Inflammation

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Use of OKT3 monoclonal antibody as induction therapy for control of rejection in liver transplantation

et al. 1995

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This report details a single center's experience with OKT3 induction immunosuppression for liver transplantation. One hundred ninety-nine consecutive, unselected adult liver recipients received OKT3 therapy for 9-10 days combined with low-dose steroids and azathioprine. Cyclosporine was begun to overlap with the last few days of OKT3 therapy. The average dose of OKT3 was 45 mg. Fifty-two patients (26.1%) experienced 57 episodes of acute rejection. The median time of onset of rejection was 18 days after grafting. Seventy-eight percent of the rejection episodes were steroid-sensitive. Recurrent rejection was uncommon and the need for OKT3 retreatment was infrequent. One year actuarial graft and patient survival was 79.7% and 82.3% respectively. Based on this evidence, it appears that OKT3 prophylaxis provides good control of acute rejection with a very low incidence of recurrent rejection.

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Chapter 19. Monoclonal Antibodies in Therapy

Heavner¹

1992

Annual Reports in Medicinal Chemistry

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Mechanisms of rejection during OKT3 therapy: Propagation and characterization of CD3 resistant allospecific cytotoxic T cells from a rejecting liver allograft

Cited by 5 publications

References 21 publications

Cytokine profiles in early rejection following OKT3 treatment in liver transplant patients

Cytokine profiles in early rejection following OKT3 treatment in liver transplant patients

Use of OKT3 monoclonal antibody as induction therapy for control of rejection in liver transplantation

Chapter 19. Monoclonal Antibodies in Therapy

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