CTLA-4-mediated regulatory phenotype of T cells in tolerant lung recipients

¹ UPRES EA 3287, Faculté de Médecine, Université de la Méditerranée, Marseille
² IFR Jean Roche, EA 2201, Marseille, France

^* To whom correspondence should be addressed. E-mail: botturikarine{at}yahoo.fr.

	Abstract

Obliterative bronchiolitis (OB) is the major cause of long-term lung allograft loss resulting from an unclear immune process occurring in the absence of donor's immune cells. We hypothesized that interactions of autologous dendritic cell (DC) with T cells could differ in OB patients compared to healthy lung transplant recipients (LTR).

Monocyte-derived DC from 14 OB and 35 non OB LTR were cultured with autologous T cells. T regulatory (Treg) cells, co-receptors, cytokine production, DC phenotype and indoleamine 2,3 dioxygenase (IDO) expression were assessed by flow cytometry. Experiments were repeated in presence of P. aeruginosa or anti-coreceptor antibodies (Abs).

DC from non OB LTR up-regulated Treg cells, CTLA-4 and IL-10. By contrast CD28 and ICOS were down-regulated concomitantly to IL-13 and IL-4. Compared to OB, non OB DC displayed an immature phenotype with lower CD80 and CD83 and higher IDO levels of expression. Stimulation by P. aeruginosa did not abolish the tolerogenic effects of DC on non OB T cells. Finally, decreased Treg cells and IL-10 production were detected when adding anti-CTLA-4 Abs in non OB LTR.

We demonstrate that DC from non OB LTR induce a tolerant T cell phenotype witch is dependent on CTLA-4 engagement.

This article has been cited by other articles:

				K. M. Williams, J. W. Chien, M. T. Gladwin, and S. Z. Pavletic Bronchiolitis Obliterans After Allogeneic Hematopoietic Stem Cell Transplantation JAMA, July 15, 2009; 302(3): 306 - 314. [Abstract] [Full Text] [PDF]