Thromboxane augmentation of alloreactive T cell function.

Published

Journal Article

Thromboxane (Tx) plays a vital role in the dysfunction and ultimate rejection of MHC-disparate renal allografts. In addition to its potent vasoconstrictory properties, in vivo studies have implied that Tx is capable of promoting immune cytotoxic T cell function within transplants. In this study, we have examined the in vitro effect of Tx inhibition on alloreactive immune cells using MHC-disparate mouse strain combinations. Coculture of either Tx-synthetase or Tx-receptor inhibitors modified the response of unprimed mouse lymphoid populations in a primary MLR, implying that Tx inhibition and not endoperoxide shunting was responsible for the modulatory effects seen. For example, B10.S lymphoid cells displayed decreased proliferation to H-2 disparate B10.A cells with Tx inhibitors present during the MLR, at pharmacologically active drug concentrations. Moreover, in vitro addition of TxA2 had an augmentory effect on the response in the primary and secondary MLR. Interleukin 2 production and percentages of T cell populations in the primary MLR were not affected by the presence of these compounds, although CD4 and CD8 expression was often increased in the treated populations. Finally, alloreactive primed effector cells also displayed reduced proliferation to specific alloantigen in a secondary MLR when Tx inhibitors were also present, although responses to IL-2 by T cells were not influenced by thromboxane inhibition. These data imply that thromboxane is an important immunoregulatory mediator capable of potentiating the function of naive and primed alloreactive immune T cell populations crucial to the rejection of the transplant.

Full Text

Duke Authors

Cited Authors

  • Ruiz, P; Rey, L; Spurney, R; Coffman, T; Viciana, A

Published Date

  • September 1992

Published In

Volume / Issue

  • 54 / 3

Start / End Page

  • 498 - 505

PubMed ID

  • 1412730

Pubmed Central ID

  • 1412730

International Standard Serial Number (ISSN)

  • 0041-1337

Digital Object Identifier (DOI)

  • 10.1097/00007890-199209000-00021

Language

  • eng

Conference Location

  • United States