HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Puliaev, R. Articles by Via, C. S. Search for Related Content PubMed PubMed Citation Articles by Puliaev, R. Articles by Via, C. S. Pubmed/NCBI databases Substance via MeSH

Differential Requirement for IFN- in CTL Maturation in Acute Murine Graft-versus-Host Disease¹

Roman Puliaev^*, Phuong Nguyen^*, Fred D. Finkelman^2, and Charles S. Via^2,3,*

^* Research Service, Baltimore Veterans Affairs Medical Center, and Division of Rheumatology and Clinical Immunology, University of Maryland School of Medicine, Baltimore, MD 21201; and Immunology Division, Veterans Affairs Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH 45267

Although IFN- is the archetypal Th1 cytokine, its role in CTL maturation is uncertain. We used an in vivo mouse model of CTL development, parent-into-F₁ acute graft-vs-host disease (AGVHD), to evaluate this issue. In AGVHD, transfer of naive parental T cells into F₁ hosts stimulates the development of allospecific CTL effectors that eliminate host lymphocytes, particularly B cells. Complete elimination of IFN-, using IFN--deficient donors and administering anti-IFN- mAb, suppressed B cell elimination, down-regulated TNF- production, and enhanced Th2 cytokine production, but did not allow the B cell expansion characteristic of chronic GVHD (CGVHD). Because complete CTL inhibition results in full-blown CGVHD that is IFN- independent, these observations indicate that IFN- elimination only partially blocks CTL development. IFN- elimination did not inhibit donor T cell engraftment or activation in the AGVHD model, but almost completely blocked Fas/Fas ligand (FasL) gene expression, protein up-regulation, and Fas/FasL-mediated CTL killing. In contrast, IFN- elimination only partially inhibited perforin gene expression and perforin-mediated CTL activity. The contributions of IFN- to CTL development were indirect, because IFN- receptor-deficient donor cells differentiated normally into allospecific CTLs. Consistent with the view that the Fas/FasL and perforin pathways each mediate CTL killing in AGVHD, the absence of both perforin and IFN- (perforin knockout donor cells and anti-IFN- mAb) converted AGVHD to CGVHD. Thus, both IFN--dependent induction of Fas/FasL and IFN--independent induction of perforin contribute to CTL-mediated elimination of host B cells in AGVHD. Suppression of both pathways is required for typical CGVHD development.

This article has been cited by other articles:

				J.-S. Delisle, L. Gaboury, M.-P. Belanger, E. Tasse, H. Yagita, and C. Perreault Graft-versus-host disease causes failure of donor hematopoiesis and lymphopoiesis in interferon-{gamma} receptor-deficient hosts Blood, September 1, 2008; 112(5): 2111 - 2119. [Abstract] [Full Text] [PDF]

				R. Puliaev, I. Puliaeva, L. A. Welniak, A. E. Ryan, M. Haas, W. J. Murphy, and C. S. Via CTL-Promoting Effects of CD40 Stimulation Outweigh B Cell-Stimulatory Effects Resulting in B Cell Elimination and Disease Improvement in a Murine Model of Lupus J. Immunol., July 1, 2008; 181(1): 47 - 61. [Abstract] [Full Text] [PDF]

				M.-E. Blais, S. Brochu, M. Giroux, M.-P. Belanger, G. Dulude, R.-P. Sekaly, and C. Perreault Why T Cells of Thymic Versus Extrathymic Origin Are Functionally Different J. Immunol., February 15, 2008; 180(4): 2299 - 2312. [Abstract] [Full Text] [PDF]

				G. Hildebrandt The lung's friend, the gut's foe Blood, August 1, 2007; 110(3): 792 - 793. [Full Text] [PDF]

				A. C. Burman, T. Banovic, R. D. Kuns, A. D. Clouston, A. C. Stanley, E. S. Morris, V. Rowe, H. Bofinger, R. Skoczylas, N. Raffelt, et al. IFN{gamma} differentially controls the development of idiopathic pneumonia syndrome and GVHD of the gastrointestinal tract Blood, August 1, 2007; 110(3): 1064 - 1072. [Abstract] [Full Text] [PDF]

				I. G. Sakala, G. Chaudhri, R. M. Buller, A. A. Nuara, H. Bai, N. Chen, and G. Karupiah Poxvirus-Encoded Gamma Interferon Binding Protein Dampens the Host Immune Response to Infection J. Virol., April 1, 2007; 81(7): 3346 - 3353. [Abstract] [Full Text] [PDF]

				V. Rus, V. Nguyen, R. Puliaev, I. Puliaeva, V. Zernetkina, I. Luzina, J. C. Papadimitriou, and C. S. Via T Cell TRAIL Promotes Murine Lupus by Sustaining Effector CD4 Th Cell Numbers and by Inhibiting CD8 CTL Activity J. Immunol., March 15, 2007; 178(6): 3962 - 3972. [Abstract] [Full Text] [PDF]