Abstract
Immune responses are by necessity highly regulated to achieve the appropriate balance of aggression and restraint. A mong the many factors involved in maintaining this balance are the interactions between accessory molecule receptorse xpressed on T cells and their ligands on antigen-presenting cells. Our studies during the past several years have focused on defining how particular accessory molecule interactions influence the activation of naive CD4+ T cells and the subsequent development of effector function. In this article, we discuss our findings on the effects of distinct accessory molecules with particular attention to the unique roles of LFA-1 and CD28 during different phases of the native CD4+ cell response.
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References
Schwartz RH: Models of T cell anergy: is there a common molecular mechanism? J Exp Med 1996: 184:1–8.
Malvey E, Telander D, Vanasek T, et al: The role of clonal anergy in the avoidance of autoimmunity: inactivation of autocrine growth without loss of effector function. Immunol Rev 1998;165:301–318.
Sprent J, Webb SR: Intrathymic andextrathymic clonal deletion of T cells. Curr Opin Immunol 1995; 7:196–205.
Alferink J, Aigner S, Reibke R, et al: Peripheral T-cell to lerance: the contribution of permissive T-cell migration into parenchymal tissues of the neonate. Immunol Rev 1999;169:255–261.
Khoruts A, Jenkins MK: Studying immunological tolerance by physically monitoring antigen-specific T cells in vivo. Ann NY Acad Sci 1996;778:72–79.
O'Garra A, Murphy K: T-cell subsets in autoimmunity. Curr Opin Immunol 1993:5:880–886.
Guerder S, Flavell RA: T-cell activation: two for T. Curr Biol 1995; 5:866–868.
Lenschow DJ, Walunas TL, Bluestone JA: CD28/B7 system of T cell co-stimulation. Annu Rev Immunol 1996:14:233–258.
Chambers CA, Allison JP: Costimulatory regulation of T cell function. Curr Opin Cell Biol 1999;11:203–210.
Zinkernagel RM, Moskophidis D, Kudig T, et al: Effector T-cell induction and T-cell memory versus peripheral deletion of T cells. Immunol Rev 1993;133: 199–223.
Stockinger B: T lymphocyte tolerance: from thymic deletion to peripheral control mechanisms. Adv Immunol 1999;71:229–265.
Sun S, Kishimoto H, Sprent J: DNA as an adjuvant: capacity of insect DNA and synthetic oligodeoxy nucleotides to augment T cell responses to specific antigen. J Exp Med 1998:187: 1145–1150.
Sum S, Zhang X, Tough DF, et al.: Type 1 interferon-mediated stimulation of T cells by CpG DNA. J Exp Med 1998:188:2335–2342.
Cai Z, Brunmark AB, Luxembourg AT, et al: Probing the activation requirements for naive CD8+ T cells with Drosophila cell transfectants as antigen presenting cells, Immunol Rev 1998:165:249–265.
Linsley PS, Ledbetter JA: The role of the CD28 receptor during T cell responses to antigen. Annu Rev Immunol 1993:11:191–212.
Powell JD, Ragheb JA, Kitagawa-Sakakida S, et al: Molecular regulation of interleukin-2 expression by CD28 co-stimulation and anergy. Immunol Rev 1998;165: 287–300.
Noel PJ, Boise LH, Green JM, et al: CD28 costi mulation prevents cell death during primary T cell activation. J Immunol 1996;157: 636–642.
Luksch CR, Winqvist O, Ozaki ME, et al.: Intercellular adhesion molecule-1 inhibits interleukin-4 production by naive T cells. Proc Natl Acad Sci USA 1999;96: 3023–3028.
Rincon M, Flavell RA: T-cell subsets: transcriptional control in the Th1/Th2 decision. Curr Biol 1997:R729–R732.
Shimizu Y, van Seventer GA, Horgan KJ, et al: Roles of adhesion molecules in T-cell recognition: fundamental similarities between four integrins on resting human T cells (LFA-1, VLA-4, VLA-5, VLA-6) in expression, binding, and costimulation. Immunol Rev 1990:114:109–143.
Damle NK, Klussman K, Linsley PS, et al: Differential costimulatory effects of adhesion molecules B7, ICAM-01, LFA-3, and VCAM-1 on resting and antigen-primed CD4+ T lymphocytes. J Immunol 1992;148:1985–1992.
Dubey C, Croft M, Swain S: Costimulatory requirements of naive CD4+T cells: ICAM-1 or B7-1 can costimulate naive CD4 T cell activation but both are required for optimum response. J Immunol 1995;155:45–57.
van Seventer GA, Newman W, Shimizu Y, et al: Analysis of T cell stimulation by superantigen plus major histocompatibility complex class II molecules or by CD3 monoclonal antibody: costimulation by purifiedadhesion ligands VCAM-1, ICAM-1, but not ELAM-1. J Exp Med 1991:174:901–913.
Coffman RL, Reiner SL: Instruction, selection, or tampering with the odds. Science 1999;284: 1283–1285.
Mosmann TR, Coffman RL: Thl and Th2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol 1989;7:145–173.
Fowell DJ, Bix M, Shinkal K, et al: Disease susceptibility and development of the cytokine repertoire in the murine Leishmania major model. Eur Cytokine Netw 1998;9:102–106.
Leitenberg D, Bottomly K: Regulation of naive T cell differentiation by varying the potency of TCR signal transduction. Semin Immunol 1999:11:283–292.
Scott B, Liblau R, Degermann S, et al: A role for non-MHC genetic polymorphism in susceptibility to spontaneous autoimmunity. Immunity 1994:1:73–82.
Hsieh C-S, Macatonia SE, O'Garra A, et al: T cell genetic background determines default T helper phenotype development in vitro. J Exp Med 1995;181:713–721.
O'Garra A, Murphy K: Role of cytokines in development of Th1 and Th2 cells. Chem Immunol 1996:63:1–13.
Murphy KM, Murphy TL, Szabo SJ, et al: Regulation of 1L-L2 receptor expression in early T-helper responses implies two phases of Th1 differentiation: capaciatance and development. Chem Immunol 1997;68: 54–69.
Seder RA, Germtain RN, Linsley PS, et al: CD28-mediated costimulation of interleukin 2 (IL-2) production plays a critical role in T cell priming for IL-4 and interferon gamma production. J Exp Med 1994;179:299–304.
Natesan M, Razi-Wolf Z, Reiser H: Costimulation of IL-4 production by murine B7-1 and B7-2 molecules. J Immunol 1996;156: 2783–2791.
Rulifson JC, Sperling AI, Fields PE, et al: CD28 costimulation promotes the production of Th2 cytokines. J Immunol 1997:158: 658–665.
Salomon B, Bluestore JA: LFA-1 interaction with ICAM-1 and ICAM-2 regulates TH2 cytokine production. J Immunol 1998;161: 5138–5142.
Kurts C, Heath WR, Carbone FR, et al: Constitutive class 1-restricted exo genous presentation of self antigens in vivo. J Exp Med 1996;184:923–930.
Kasuga A, Maruyama T, Takel I, et al: The role of cytotoxic macro phages in non-obese diabetic mice: cytotoxicity against murine mastocytoma and beta-cell lines. Diabetologia 1993;36:1252–1257.
Jun HS, Yoon, CS, Zbytnuik, L. et al.: The role of macrophages in T cell-mediated autoimmune diabetes in nonobese diabetic mice. J Exp Med 1999;189: 347–358.
Zlotnik A, Morales J, Hedrick JA: Recent advances in chemokines and chemokinereceptors. Crit Rev Immunol 1999;19:1–47.
Webb SR, Morris C, Sprent J: Extrathymic tolerance of mature T cells: clonal elimination as a consequence of immunity. Cell 1990;63:1249–1256.
Jones LA, Chin LT, Longo DL, et al.: Peripheral clonal elimination of functional T cells. Science 1990;250:1726–1729.
Kawabe Y, Ochi A: Programmed cell death and extrathymic reduction of Vβ8+ CD4+ T cells in mice tolerant to Staphylococcus aureus enterotoxin B. Nature 1991;349: 245–248.
Janeway CA Jr: Selective elements for the Vβ region of the T cell receptor: Mls and the bacterial toxic mitogens. Adv Immunol 1991;50:1–53.
Henman A, Kappler JW, Marrack P, et al.: Superantigens: mechanism of T cell stimulation and role in immune responses. Annu Rev Immunol 1991;9:745–772.
Li H, Llera A, Malchiodi EL, et al.: The structural basis of T cell activation by superantigens. Annu Rev Immunol 1999;17:435–466.
Ahmed R, Sprent J: Immunological memory. Immunologist 1999;7:23–26.
Webb SR, Sprent J: Factors controlling the reactivity of immature and mature T cells to Mls antigens in vivo. Immunol Rev 1993;131: 169–188.
Mehal WZ, Juedes AE, Crispe IN: Selective retention of activated CD8+ T cells by the normal liver. J Immunol 1999;163:3202–3210.
Sprent J: Fate of H-2-activated T lymphocytes in syngeneic hosts. 1. Fate in lymphoid tissues and intestines traced with 3H-thymidine, 125I-deoxyuridine and 51chromium. Cell Immunol 1976;21:278–302.
van Parijs L, Perez VL, Abbas AK: Mechanisms of peripheral T cell tolerance. Novartis Found Symp 1998;215:5–14 (discussion 14–20, 33–40).
Chinnaiyan AM, Dixit VM: Portrait of an executioner: the molecular mechanism of FAS/APO-1-induced apoptosis Semin Immunol 1997;9:69–76.
Nagata S: A death factor—the other side of the coin. Behring Inst Mitt 1996;97:1–11.
Bonfoco E, Stuart PM, Brunner T, et al.: Inducible nonlymphoid expression of Fas ligand is responsible for superantigen-induced peripheral deletion of T cells. Immunity 1998;9:711–720.
Ware CF, Van Arsdale S, Van Arsdale TL: Apoptosis mediated by the TNF-related cytokine and receptor families. J Cell Biochem 1996;60:47–55.
Gravestein LA, Borst J: Tumor necrosis factor receptor family members in the immune system. Semin Immunol 1998;10: 423–434.
Groux H, Bigler M, de Vries JE, et al.: Interleukin-10 induces a long-term antigen-specific anergic state in human CD4+ T cells. J Exp Med 1996;184:19–29.
Sloan-Lancaster J, Evavold BD, Allen PM: Induction of T-cell anergy by altered T-cell receptor ligand on live antigen presenting cells. Nature 1993;363: 156–159.
Mueller DL, Jenkins MK, Schwartz RH: Clonal expansion versus functional clonal inactivation: a costimulatory signalling pathway determines the outcome of T cell antigen receptor occupancy. Annu Rev Immunol 1989; 7:445–480.
Jenkins MK, Mueller D, Schwartz