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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zhan, Y. Articles by Lew, A. M. Search for Related Content PubMed PubMed Citation Articles by Zhan, Y. Articles by Lew, A. M. Pubmed/NCBI databases Substance via MeSH

CD4 Help-Independent Induction of Cytotoxic CD8 Cells to Allogeneic P815 Tumor Cells Is Absolutely Dependent on Costimulation¹

Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Parkville, Australia

Mice made transgenic (Tg) for a rat anti-mouse CD4 Ab (GK mice) represent a novel CD4-deficient model. They not only lack canonical CD4 cells in the periphery, but also lack the residual aberrant Th cells that are found in CD4^-/- mice and MHC class II^-/- mice. To analyze the role of CD4 help and costimulation for CTL induction against alloantigens, we have assessed the surface and functional phenotype of CD8 cells in vivo (e.g., clearance of allogeneic P815 cells) and in vitro. In our CD4-deficient GK mice, CTL responses to allogeneic P815 cells were induced, albeit delayed, and were sufficient to eliminate P815 cells. Induction of CTL and elimination of allogeneic P815 cells were inhibited both in the presence and absence of CD4 cells by temporary CD40 ligand blockade. This indicated that direct interaction of CD40/CD40L between APCs and CD8 cells may be an accessory signal in CTL induction (as well as the indirect pathway via APC/CD4 interaction). Furthermore, whereas in CTLA4Ig single Tg mice P815 cells were rejected promptly, in the double Tg GK/CTLA4Ig mice CTL were not induced and allogeneic P815 cells were not rejected. These findings suggest that CD40/CD40L is involved in both CD4-dependent and CD4-independent pathways, and that B7/CD28 is pivotal in the CD4-independent pathway of CTL induction against allogeneic P815 cells.

This article has been cited by other articles:

				A. E. Gelman, M. Okazaki, J. Lai, C. G. Kornfeld, F. H. Kreisel, S. B. Richardson, S. Sugimoto, J. R. Tietjens, G. A. Patterson, A. S. Krupnick, et al. CD4+ T Lymphocytes Are Not Necessary for the Acute Rejection of Vascularized Mouse Lung Transplants J. Immunol., April 1, 2008; 180(7): 4754 - 4762. [Abstract] [Full Text] [PDF]

				M. P. Tan, J. Pedersen, Y. Zhan, A. M. Lew, M. J. Pearse, O. L. C. Wijburg, and R. A. Strugnell CD8+ T Cells Are Associated with Severe Gastritis in Helicobacter pylori- Infected Mice in the Absence of CD4+ T Cells Infect. Immun., March 1, 2008; 76(3): 1289 - 1297. [Abstract] [Full Text] [PDF]

				Y. Zhai, Y. Wang, Z. Wu, and J. W. Kupiec-Weglinski Defective Alloreactive CD8 T Cell Function and Memory Response in Allograft Recipients in the Absence of CD4 Help J. Immunol., October 1, 2007; 179(7): 4529 - 4534. [Abstract] [Full Text] [PDF]

				P. H. Horne, M. A. Koester, K. Jayashankar, K. E. Lunsford, H. L. Dziema, and G. L. Bumgardner Disparate Primary and Secondary Allospecific CD8+ T Cell Cytolytic Effector Function in the Presence or Absence of Host CD4+ T Cells J. Immunol., July 1, 2007; 179(1): 80 - 88. [Abstract] [Full Text] [PDF]

				M. G. H. Hernandez, L. Shen, and K. L. Rock CD40-CD40 Ligand Interaction between Dendritic Cells and CD8+ T Cells Is Needed to Stimulate Maximal T Cell Responses in the Absence of CD4+ T Cell Help J. Immunol., March 1, 2007; 178(5): 2844 - 2852. [Abstract] [Full Text] [PDF]

				N. E. Blachere, H. K. Morris, D. Braun, H. Saklani, J. P. Di Santo, R. B. Darnell, and M. L. Albert IL-2 Is Required for the Activation of Memory CD8+ T Cells via Antigen Cross-Presentation. J. Immunol., June 15, 2006; 176(12): 7288 - 7300. [Abstract] [Full Text] [PDF]

				B. Lim, R. M. Sutherland, Y. Zhan, G. Deliyannis, L. E. Brown, and A. M. Lew Targeting CD45RB alters T cell migration and delays viral clearance Int. Immunol., February 1, 2006; 18(2): 291 - 300. [Abstract] [Full Text] [PDF]

				A. P. Uldrich, N. Y. Crowe, K. Kyparissoudis, D. G. Pellicci, Y. Zhan, A. M. Lew, P. Bouillet, A. Strasser, M. J. Smyth, and D. I. Godfrey NKT Cell Stimulation with Glycolipid Antigen In Vivo: Costimulation-Dependent Expansion, Bim-Dependent Contraction, and Hyporesponsiveness to Further Antigenic Challenge J. Immunol., September 1, 2005; 175(5): 3092 - 3101. [Abstract] [Full Text] [PDF]

				J. Colgan, M. Asmal, B. Yu, and J. Luban Cyclophilin A-Deficient Mice Are Resistant to Immunosuppression by Cyclosporine J. Immunol., May 15, 2005; 174(10): 6030 - 6038. [Abstract] [Full Text] [PDF]

				T. Nakamura, K.-H. Sonoda, D. E. Faunce, J. Gumperz, T. Yamamura, S. Miyake, and J. Stein-Streilein CD4+ NKT Cells, But Not Conventional CD4+ T Cells, Are Required to Generate Efferent CD8+ T Regulatory Cells Following Antigen Inoculation in an Immune-Privileged Site J. Immunol., August 1, 2003; 171(3): 1266 - 1271. [Abstract] [Full Text] [PDF]

				Y. Zhai, L. Meng, R. W. Busuttil, M. H. Sayegh, and J. W. Kupiec-Weglinski Activation of Alloreactive CD8+ T Cells Operates Via CD4-Dependent and CD4-Independent Mechanisms and Is CD154 Blockade Sensitive J. Immunol., March 15, 2003; 170(6): 3024 - 3028. [Abstract] [Full Text] [PDF]

				D. J. Shedlock, J. K. Whitmire, J. Tan, A. S. MacDonald, R. Ahmed, and H. Shen Role of CD4 T Cell Help and Costimulation in CD8 T Cell Responses During Listeria monocytogenes Infection J. Immunol., February 15, 2003; 170(4): 2053 - 2063. [Abstract] [Full Text] [PDF]

				Y. Zhan, J. F. Purton, D. I. Godfrey, T. J. Cole, W. R. Heath, and A. M. Lew Without peripheral interference, thymic deletion is mediated in a cohort of double-positive cells without classical activation PNAS, February 4, 2003; 100(3): 1197 - 1202. [Abstract] [Full Text] [PDF]

				H.-M. Hu, H. Winter, J. Ma, M. Croft, W. J. Urba, and B. A. Fox CD28, TNF Receptor, and IL-12 Are Critical for CD4-Independent Cross-Priming of Therapeutic Antitumor CD8+ T Cells J. Immunol., November 1, 2002; 169(9): 4897 - 4904. [Abstract] [Full Text] [PDF]

				Y. Zhai, L. Meng, F. Gao, R. W. Busuttil, and J. W. Kupiec-Weglinski Allograft Rejection by Primed/Memory CD8+ T Cells Is CD154 Blockade Resistant: Therapeutic Implications for Sensitized Transplant Recipients J. Immunol., October 15, 2002; 169(8): 4667 - 4673. [Abstract] [Full Text] [PDF]

				R. E. Miller, J. Jones, T. Le, J. Whitmore, N. Boiani, B. Gliniak, and D. H. Lynch 4-1BB-Specific Monoclonal Antibody Promotes the Generation of Tumor-Specific Immune Responses by Direct Activation of CD8 T Cells in a CD40-Dependent Manner J. Immunol., August 15, 2002; 169(4): 1792 - 1800. [Abstract] [Full Text] [PDF]

				R. M. Sutherland, B. S. McKenzie, Y. Zhan, A. J. Corbett, A. Fox-Marsh, H. M. Georgiou, L. C. Harrison, and A. M. Lew Anti-CD45RB antibody deters xenograft rejection by modulating T cell priming and homing Int. Immunol., August 1, 2002; 14(8): 953 - 962. [Abstract] [Full Text] [PDF]

				Y. Zhai, X.-D. Shen, F. Gao, A. J. Coito, B. A. Wasowska, A. Salama, I. Schmitt, R. W. Busuttil, M. H. Sayegh, and J. W. Kupiec-Weglinski The CD154-CD40 T Cell Costimulation Pathway Is Required for Host Sensitization of CD8+ T Cells by Skin Grafts Via Direct Antigen Presentation J. Immunol., August 1, 2002; 169(3): 1270 - 1276. [Abstract] [Full Text] [PDF]

				Y.-G. Yang, J. Qi, M.-G. Wang, and M. Sykes Donor-derived interferon gamma separates graft-versus-leukemia effects and graft-versus-host disease induced by donor CD8 T cells Blood, May 13, 2002; 99(11): 4207 - 4215. [Abstract] [Full Text] [PDF]

				Y. Zhan, J. L. Brady, R. M. Sutherland, and A. M. Lew Without CD4 Help, CD8 Rejection of Pig Xenografts Requires CD28 Costimulation But Not Perforin Killing J. Immunol., December 1, 2001; 167(11): 6279 - 6285. [Abstract] [Full Text] [PDF]