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 Google Scholar Google Scholar Articles by Horne, P. H. Articles by Bumgardner, G. L. Search for Related Content PubMed PubMed Citation Articles by Horne, P. H. Articles by Bumgardner, G. L.

Disparate Primary and Secondary Allospecific CD8⁺ T Cell Cytolytic Effector Function in the Presence or Absence of Host CD4⁺ T Cells¹

Phillip H. Horne, Mitchel A. Koester^*, Kartika Jayashankar^*, Keri E. Lunsford, Heather L. Dziema^* and Ginny L. Bumgardner^2,*,

^* Department of Surgery, Comprehensive Transplant Center, Ohio State University Medical Center, Columbus, OH 43210; and Integrated Biomedical Science Graduate Program, College of Medicine, Ohio State University, Columbus, OH 43210

The role of CD4⁺ T cells in promoting CD8⁺ T cell effector activity in response to transplant Ags in vivo has not been reported. We used a hepatocellular allograft model known to initiate both CD4-dependent and CD4-independent rejection responses to investigate the contribution of CD4⁺ T cells to the development, function, and persistence of allospecific CD8⁺ T cell effectors in vivo. Complete MHC-mismatched hepatocellular allografts were transplanted into C57BL/6 (CD4-sufficient) or CD4 knockout (CD4-deficient) hosts. The development of in vivo allospecific cytotoxicity was determined by clearance of CFSE-labeled target cells. CD8⁺ T cell cytotoxic effector activity was enhanced in response to allogeneic hepatocellular grafts with a greater magnitude of allocytotoxicity and a prolonged persistence of CTL effector activity in CD4-sufficient hosts compared with CD4-deficient hosts. Cytolytic activity was mediated by CD8⁺ T cells in both recipient groups. In response to a second hepatocyte transplant, rejection kinetics were enhanced in both CD4-sufficient and CD4-deficient hepatocyte recipients. However, only CD4-sufficient hosts developed recall CTL responses with an augmented magnitude and persistence of allocytotoxicity in comparison with primary CTL responses. These studies show important functional differences between alloreactive CD8⁺ T cell cytolytic effectors that mature in vivo in the presence or absence of CD4⁺ T cells.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported in part by grants from the American Society of Transplantation Basic Science Physician Scientist Award (to P.H.H.), Roche Organ Transplantation Research Foundation (to G.L.B.), the American Society of Transplant Surgeons (to G.L.B.), and National Institutes of Health DK072262 (to G.L.B.).

² Address correspondence and reprint requests to Dr. Ginny L. Bumgardner, Ohio State University Medical Center, Department of Surgery, Division of Transplant, 1654 Upham Drive, 373 Means Hall, Columbus, OH 43210-1250. E-mail address: ginny.bumgardner{at}osumc.edu

³ Abbreviations used in this paper: KO, knockout; FasL, Fas ligand; GIC, graft-infiltrating cell; hA1AT, human -1 antitrypsin; MST, median survival time.