CD28-B7 T cell costimulatory blockade by CTLA4Ig in the rat renal allograft model

Inhibition of cell-mediated and humoral immune responses in vivo

Enver Akalin, Anil Chandraker, Mary E. Russell, Laurence A. Turka, Wayne W. Hancock, Mohamed H. Sayegh

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Blocking CD28-B7 T-cell costimulation by CTLA4Ig induces tolerance to rat renal allografts and inhibits Th1, but spares Th2, cytokines. We now report on the mechanisms of CD28-B7 blockade in this model. Lymphocytes from CTLA4Ig-treated animals showed significant reduction of mixed lymphocyte response, as well as antidonor cytotoxic T-cell effector function, as compared with rejecting controls. Flow cytometry studies on sera of renal allograft recipients showed complete inhibition of antidonor humoral responses by CTLA4Ig. Analysis by reverse transcriptase-polymerase chain reaction and immunohistology showed that intragraft macrophage products, monocyte chemoattractant protein-1 and inducible nitric oxide synthase, were reduced by CTLA4Ig therapy. Immunohistologic studies also showed reduced intragraft macrophage infiltration and decreased staining for the fibrogenic and mitogenic growth factor, transforming growth factor-β. These results indicate that CD28-B7 blockade inhibits cell-mediated and humoral immune responses, and suggest that strategies targeting T-cell costimulation may provide a novel approach to prevent chronic allograft rejection.

Original languageEnglish (US)
Pages (from-to)1942-1945
Number of pages4
JournalTransplantation
Volume62
Issue number12
DOIs
StatePublished - Dec 27 1996
Externally publishedYes

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Humoral Immunity
Allografts
T-Lymphocytes
Kidney
Macrophages
Lymphocytes
Chemokine CCL2
Transforming Growth Factors
Nitric Oxide Synthase Type II
Reverse Transcriptase Polymerase Chain Reaction
Intercellular Signaling Peptides and Proteins
Flow Cytometry
Staining and Labeling
Cytokines
Serum
Therapeutics

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

CD28-B7 T cell costimulatory blockade by CTLA4Ig in the rat renal allograft model : Inhibition of cell-mediated and humoral immune responses in vivo. / Akalin, Enver; Chandraker, Anil; Russell, Mary E.; Turka, Laurence A.; Hancock, Wayne W.; Sayegh, Mohamed H.

In: Transplantation, Vol. 62, No. 12, 27.12.1996, p. 1942-1945.

Research output: Contribution to journalArticle

Akalin, Enver ; Chandraker, Anil ; Russell, Mary E. ; Turka, Laurence A. ; Hancock, Wayne W. ; Sayegh, Mohamed H. / CD28-B7 T cell costimulatory blockade by CTLA4Ig in the rat renal allograft model : Inhibition of cell-mediated and humoral immune responses in vivo. In: Transplantation. 1996 ; Vol. 62, No. 12. pp. 1942-1945.
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