A unique syndrome of immunodeficiency and autoimmunity associated with absent T cell CD2 expression

Springer Science and Business Media LLC - Tập 14 - Trang 359-367 - 1994
Michael C. Sneller1, Eli M. Eisenstein2, Michael Baseler3, H. Clifford Lane1, Eileen T. Donoghue1, Judith Falloon1
1Laboratory of Immunoregulation, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda
2Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda
3Cancer Research and Development Center-National Cancer Institute, Clinical Immunology Services, Program Resources Incorporated, DynCorp, Frederick, Frederick

Tóm tắt

CD2 is a glycoprotein expressed on the surface of human T cells that mediates adhesion between T cells and antigen presenting cells. CD2 also functions in concert with the T cell receptor to transduce signals that lead to T cell activation. The CD8 and CD4 molecules are transmembrane glycoproteins that are expressed on mutually exclusive populations of mature T cells and bind to determinants on major histocompatibility complex class I and class II molecules respectively. Like CD2, CD4 and CD8 function to promote adhesion between T cells and antigen presenting cells and potentiate signaling via the T cell receptor. We studied a patient with idiopathic lymphopenia and disseminated infection withMycobacterium avium. The patient also suffered from recurrent deep venous thrombosis in association with anticardiolipin and anti-DNA antibodies. Peripheral blood T cells from this patient were polyclonal and expressed no detectable CD2 RNA or protein as determined by northern blotting, immunofluorescent staining with anti-CD2 antibodies, and failure to form rosettes with sheep red blood cells. In addition, the majority (85%) of this patient's T cells did not express either CD4 or CD8 but did express the α/β T cell receptor. T cells from this patient failed to respond to stimulation with alloantigen or specific antigen. In contrast, there was a normal response to stimulation with immobilized anti-CD3 antibody. The clinical and immunologic findings in this patient providein vivo evidence that the accessory molecules CD2, CD4, and CD8 play important roles in the regulation of normal human T cell activation.

Tài liệu tham khảo

Rothbard J, Gefter M: Interactions between immunogenic peptides and MHC proteins. Annu Rev Immunol 9:527–565, 1991 Bierer B, Sleckman B, Ratnofsky S, Burakoff S: The biologic roles of CD2, CD4, and CD8 in T cell activation. Annu Rev Immunol 7:579–599, 1989 Boyum A: Separation of blood leucocytes, granulocytes and lymphocytes. Tissue Antigens 4:269–275, 1974 Geppert TD, Lipsky P: Accessory cell independent proliferation of human T4 cells stimulated by immobilized monoclonal antibodies to CD3. J Immunol 138:1660–1668, 1987 Meuer SC, Hussey RE, Fabbi M, Fox D, Acuto O, Fitzgerald KA, Hodgdon JC, Protentis JP, Schlossman SF, Reinherz EL: An alternative pathway of T-cell activation: A functional role for the 50 kd T11 sheep erythrocyte receptor protein. Cell 36:897–906, 1984 Sneller MC, Straus SE, Jaffe ES, Jaffe JS, Fleisher TA, Stetler SM, Strober W: A novel lymphoproliferative/autoimmune syndrome resembling murine lpr/gld disease. J Clin Invest 90:334–341, 1992 CDC: Guidelines for the performance of CD4 T cell determinations in persons with human Immunodeficiency virus infections. Morbid Mortal Week Rep 41:RR-8, 1992 Itoh N, Yonehara S, Ishii A, Yonehara M, Mizushima S, Sameshima M, Hase A, Seto Y, Nagata S: The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis. Cell 66:233–243, 1991 Dorsett B, Cronin W, Chuma V, Ioachim HL: Antilymphocyte antibodies in patients with the acquired immune deficiency syndrome. Am J Med 78:621–629, 1985 Siu G, Clark SP, Yoshikai Y, Malissen M, Yanagi Y, Strauss E, Mak TW, Hood L: The human T cell antigen receptor is encoded by variable, diversity, and joining gene segments that rearrange to generate a complete V gene. Cell 37:393–403, 1984 Sewell WA, Brown MH, Dunne J, Owen MJ, Crumpton MJ: Molecular cloning of the human T-lymphocyte surface CD2 antigen. Proc Natl Acad Sci USA 83:8718–8722, 1986 Cohen PL, Eisenberg RA: Lpr and gld: single gene models of systemic autoimmunity and lymphoproliferative disease. Annu Rev Immunol 9:243–269, 1991 Watanabe-Fukunaga R, Brannan CI, Copeland NG, Jenkins NA, Nagata S: Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis. Nature 356:314–317, 1992 Miyawaki T, Uehara T, Nibu R, Tsuji T, Yachie A, Yonehara S, Taniguchi N: Differential expression of apoptosis-related Fas antigen on lymphocyte subpopulations in human peripheral blood. J Immunol 149:3753–3758, 1992 Owen SL, Yonehara S, Crump W, Grimm EA: DNA fragmentation and cell death is selectively triggered in activated human lymphocytes by Fas antigen engagement. Cell Immunol 140:197–205, 1992 Lang G, Wotton D, Owen MJ, Sewell WA, Brown MH, Mason DY, Crumpton MJ, Kioussis D: The structure of the human CD2 gene and its expression in transgenic mice. EMBO J 7:1675–1682, 1988 Moingeon P, Chang HC, Sayre PH, Clayton LK, Alcover A, Gardner P, Reinherz EL: The structural biology of CD2. Immunol Rev 111:111–141, 1989 Shivakumar S, Tsokos G, Datta S: T cell receptor alpha/beta expressing double negative and CD4+ T helper cells in humans augment the production of pathogenic anti-DNA autoantibodies associated with lupus nephritis. J Immunol 143:103–112, 1989 de la Hera A, Toribio M, Marquez C, C M: IL-2 promotes growth and cytolytic activity in human T3+4−8-thymocytes. Proc Natl Acad Sci USA 82:6268–6271, 1985 Groh V, Fabbi M, Hochstenbach F, Maziarz R: Double negative (CD4−8-) lymphocytes bearing T cell receptor alpha and beta chains in normal human skin. Proc Natl Acad Sci USA 86:5059–5063, 1989 Wirt D, Brooks E, Vaidya S, Klimpel G, Waldman T, Goldblum R: A novel T lymphocyte population in combined immunodeficiency with features of graft-versus-host disease. N Engl J Med 321:370–374, 1989 Illum N, Ralfkiaer E, Pallesin G, Geisler C: Phenotypic and functional characterization of double-negative alpha/beta T-cell receptor positive cells from an immunodeficient patient. Scand J Immunol 34:635–645, 1991 Kabelitz D, Conradt P, Schondelmaier S, Wagner H, Haars R: A novel subset of CD2-, CD3/Tcell receptor alpha/beta+ human peripheral blood T cells. J Exp Med 170:559–569, 1989 Kabelitz D, Conradt P: Identification of CD2−/CD3+ T cells in fetal human tissue. J Exp Med 168:1941–1946, 1988 Krensky A, Robbins E, Springer T, Burakoff S: LFA1, LFA2, and LFA3 antigens are involved in CTL-target conjugation. J Immunol 132:2180–2182, 1984 Verbi W, Greaves M, Schneider C, Koubek K, Janossy G, Stein H, Kung P, Goldstein G: Monoclonal antibodies OKT11 and OKT11A have pan-T reactivity and block sheep erythrocyte receptors. J Immunol 12:81–86, 1982 Shaw S, Luce GE, Quinones R, Gress RE, Springer TA, Sanders ME: Two antigen-independent adhesion pathways used by human cytotoxic T-cell clones. Nature 323:262–264, 1986 Bierer B, Peterson A, Gorga J, Herrmann S, Burakoff S: Synergistic T cell activation via the physiological ligands for CD2 and the T cell receptor. J Exp Med 168:1145–1156, 1988 Yang SY, Chouaib S, Dupont B: A common pathway for T lymphocyte activation involving both the CD3-Ti complex and CD2 sheep erythrocyte receptor determinants. J Immunol 137:1097–1100, 1986 Krensky AM, Sanchez MF, Robbins E, Nagy JA, Springer TA, Burakoff SJ: The functional significance, distribution, and structure of LFA-1, LFA-2, and LFA-3: Cell surface antigens associated with CTL-target interactions. J Immunol 131:611–616, 1983 Sanders M, Makgoba M, Sharrow S, Stephany D, Springer T, Young H, Shaw S: Human memory T lymphocytes express increased levels of three cell adhesion molecules (LFA-3, CD2, and LFA-1) and three other molecules (UCHl1, CDw29, and Pgp-1) and have enhanced IFN-gamma production. J Immunol 140:1401–1407, 1988 Moingeon P, Chang HC, Wallner BP, Stebbins C, Frey AZ, Reinherz EL: CD2-mediated adhesion facilitates T lymphocyte antigen recognition function. Nature 339:312–314, 1989 Veillette A, Bookman MA, Horak EM, Bolen JB: The CD4 and CD8 T cell surface antigens are associated with the internal membrane tyrosine-protein kinase p56lck. Cell 55: 301–308, 1988 Rudd CE, Trevillyan JM, Dasgupta JD, Wong LL, Schlossman SF: The CD4 receptor is complexed in detergent lysates to a protein-tyrosine kinase (pp58) from human T lymphocytes. Proc Natl Acad Sci USA 85:5190–5194, 1988 Marth JD, Peet R, Krebs EG, Perlmutter RM: A lymphocyte-specific protein-tyrosine kinase gene is rearranged and overexpressed in the murine T cell lymphoma LSTRA. Cell 43:393–404, 1985 Janeway C: The T cell receptor as a multicomponent signalling machine: CD4/CD8 coreceptors and CD45 in T cell activation. Annu Rev Immunol 10:645–674, 1992 Haynes B, Denning S, Le P, Singer K: Human intrathymic T cell differentiation. Immunology 2:67–77, 1990 Fox DA, Hussey RE, Fitzgerald KA, Bensussan A, Daley JF, Schlossman SF, Reinherz EL: Activation of human thymocytes via the 50KD T11 sheep erythrocyte binding protein induces the expression of interleukin 2 receptors on both T3+ and T3-populations. J Immunol 134:330–335, 1985 Vollger LW, Tuck DT, Springer TA, Haynes BF, Singer KH: Thymocyte binding to human thymic epithelial cells is inhibited by monoclonal antibodies to CD-2 and LFA-3 antigens. J Immunol 138:358–363, 1987 Teh H, Kishi H, Scott B, von Boehmer H: Deletion of autospecific T cells in T cell receptor (TCR) transgenic mice spares cells with normal TCR levels and low levels of CD8 molecules. J Exp Med 169:795–806, 1989