Acquired cd40-ligand deficiency in chronic lymphocytic leukemia
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ABSTRACT Patients with B-cell chronic lymphocytic leukemia (CLL) acquire an immunodeficiency with many characteristics similar to those of persons with inherited defects in the gene encoding
the CD40-ligand (CD154). We found that the blood and splenic CD4+ T cells of patients with CLL failed to express surface CD154 after CD3 ligation. However, using an enzyme-linked
immunosorbent assay (ELISA)-based quantitative competitive polymerase chain reaction (PCR), we noted that CD3 ligation could induce such T cells to express CD154 messenger RNA at levels
similar to that of CD3-activated T cells from normal donors. Moreover, addition of increasing numbers of CLL B cells to activated normal donor T cells rapidly resulted in progressively
greater down-modulation of CD154. Such down-modulation of CD154 could be blocked by addition of CD40 monoclonal antibody to cultures _in vitro_. We propose that leukemia cell-mediated
down-modulation of CD154 on activated T cells accounts for some of the acquired immune defects of patients with CLL. Access through your institution Buy or subscribe This is a preview of
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BY FLOW CYTOMETRY Article Open access 29 February 2024 DETECTION OF CLCF1 PROTEIN EXPRESSION BY FLOW CYTOMETRY Article Open access 10 June 2024 REFERENCES * Roy, M., Waldschmidt, T.,
Aruffo, A., Ledbetter, J.A. & Noelle, R.J. The regulation of the expression of gp39, the CD40 ligand, on normal and cloned CD49+ T cells. _J. Immunol._ 151, 2497–2510 (1993). CAS PubMed
Google Scholar * Castle, B.E., Kishimoto, K., Steams, C., Brown, M.L. & Kehry, M.R. Regulation of expression of the ligand for CD40 on T helper lymphocytes. _J. Immunol._ 151,
1777–1788 (1993). CAS PubMed Google Scholar * Banchereau, J. _et al_. The CD40 antigen and its ligand. _Annu. Rev. Immunol._ 12, 881–922 (1994). Article CAS Google Scholar * Clark,
E.A. & Ledbetter, J.A. How B and T cells talk to each other. _Nature_ 367, 425–428 (1994). Article CAS Google Scholar * Van den Eertwegh, A.J. _et al_. In vivo CD40-gp39 interactions
are essential for thymus-dependent humoral immunity. I. In vivo expression of CD40 ligand, cytokines and antibody production delineates sites of cognate T-B Cell interactions. _J. Exp. Med._
178, 1555–1565 (1993). Article CAS Google Scholar * Casamayor-Palleja, M., Khan, M. & MacLennan, I.C. A subset of CD4+ memory T cells contains preformed CD40 ligand that is rapidly
but transiently expressed on their surface after activation through the T Cell receptor complex. _J. Exp. Med._ 181, 1293–1301 (1995). Article CAS Google Scholar * Han, S. _et al_.
Cellular interaction in germinal centers: Roles of CD40 ligand and B7-2 in established germinal centers. _J. Immunol._ 155, 556–567 (1995). CAS PubMed Google Scholar * Aruffo, A. _et al_.
The CD40 ligand, gp39, is defective in activated T cells from patients with X-linked hyper-IgM syndrome. _Cell_ 72, 291–300 (1993). Article CAS Google Scholar * Allen, R.C. _et al_. CD40
ligand gene defects responsible for X-linked hyper-IgM syndrome. _Science_ 259, 990–993 (1993). Article CAS Google Scholar * DiSanto, J.P., Bonnefoy, J.Y., Gauchat, J.F., Fischer, A.
& de Saint Basile, G. CD40 ligand mutations in X-iinked immunodeficiency with hyper-IgM. _Nature_ 361, 541–543 (1993). Article CAS Google Scholar * Korthauer, U. _et al_. Defective
expression of T-Cell CD40 ligand causes X-linked immunodeficiency with hyper-IgM. _Nature_ 361, 539–541 (1993). Article CAS Google Scholar * Grewal, I.S., Xu, J. & Flavell, R.A.
Impairment of antigen-specific T-Cell priming in mice lacking CD40 ligand. _Nature_ 378, 617–620 (1995). Article CAS Google Scholar * Kipps, T.J. Chronic lymphocytic leukemia and related
diseases. in _William's Hematology_. (eds. Beutler, E., Lichtman, M.A., Coller, B.S. & Kipps, T.J.) 1017–1039 (McGraw-Hill, Inc., New York, 1995). Google Scholar * Hamblin, T.J.,
Oscier, D.G. & Young, B.J. Autoimmunity in chronic lymphocytic leukaemia. _J. Clin. Pathol._ 39, 713–716 (1986). Article CAS Google Scholar * Westbrook, C.A. & Golde, D.W.
Clinical problems in hairy Cell leukemia: Diagnosis and management. _Semin. Oncol._ 11, 514–522 (1984). CAS PubMed Google Scholar * Rosen, F.S., Cooper, M.D. & Wedgwood, R.J. The
primary immunodeficiencies. _N. Engl. J. Med._ 333, 431–440 (1995). Article CAS Google Scholar * Lucivero, G., Prchal, J.T., Lawton, A.R., Antonaci, S. & Bonomo, L. Abnormal T-Cell
functions in B-Cell chronic lymphocytic leukemia do not imply T-lymphocyte involvement in the leukemic process: Report of a case with demonstrated “polyclonality” of T lymphocytes. _J. Clin.
Immunol._ 3, 111–116 (1983). Article CAS Google Scholar * Han, T. _et al_. Lack of autologous mixed lymphocyte reaction in patients with chronic lymphocytic leukemia: Evidence for
autoreactive T-Cell dysfunction not correlated with phenotype, karyotype, or clinical status. _Blood_ 60, 1075–1081 (1982). CAS PubMed Google Scholar * Kay, N.E. & Kaplan, M.E.
Defective T Cell responsiveness in chronic lymphocytic leukemia: Analysis of activation events. _Blood_ 67, 578–581 (1986). CAS PubMed Google Scholar * Kay, N.E. & Kaplan, M.E.
Defective expression of T Cell antigens in chronic lymphocytic leukaemia: Relationship to T Cell dysfunction. _Br. J. Haematol._ 57, 105–111 (1984). Article CAS Google Scholar *
Ayanlar-Batuman, O., Ebert, E. & Hauptman, S.P. Defective interleukin-2 production and responsiveness by T cells in patients with chronic lymphocytic leukemia of B Cell variety. _Blood_
67, 279–284 (1986). CAS PubMed Google Scholar * Fernandez, L.A., MacSween, J.M. & Langley, G.R. T Cell function in untreated B Cell chronic lymphocytic leukemia. _Cancer_ 39,
1168–1174 (1977). Article CAS Google Scholar * Platsoucas, C.D. _et al_. Defective spontaneous and antibody-dependent cytotoxicity mediated by E-rosette-positive and E-rosette-negative
cells in untreated patients with chronic lymphocytic leukemia: Augmentation by in vitro treatment with interferon. _J. Immunol._ 125, 1216–1223 (1980). CAS PubMed Google Scholar *
Callery, R.T. _et al_. Functional abnormalities associated with T lymphocytes from patients with chronic lymphocytic leukemia. _Clin. Immunol. Immunopathol._ 17, 451–458 (1980). Article CAS
Google Scholar * Semenzato, G., Pezzutto, A., Agostini, C., Albertin, M. & Gasparotto, G. T-lymphocyte subpopulations in chronic lymphocytic leukemia: A quantitative and functional
study. _Cancer_ 48, 2191–2197 (1981). Article CAS Google Scholar * Matutes, E., Wechsler, A., Gomez, R., Cherchi, M. & Catovsky, D. Unusual T-Cell phenotype in advanced B-chronic
lymphocytic leukaemia. _Br. J. Haematol._ 49, 635–642 (1981). Article CAS Google Scholar * Totterman, T.H., Carlsson, M., Simonsson, B., Bengtsson, M. & Nilsson, K. T-Cell activation
and subset patterns are altered in B-CLL and correlate with the stage of the disease. _Blood_ 74, 786–792 (1989). CAS PubMed Google Scholar * Patel, H.R., Oshiba, A., Jeppson, J.D. &
Gelfand, E.W. Differential expression of CD40 ligand on T Cell subsets: Implications for different roles of CD45RA+ and CD45RO+ cells in IgE production. _J. Immunol._ 156, 1781–1787 (1996).
CAS PubMed Google Scholar * Lotz, M., Ranheim, E. & Kipps, T.J. Transforming growth factor beta as endogenous growth inhibitor of chronic lymphocytic leukemia B cells. _J. Exp. Med._
179, 999–1004 (1994). Article CAS Google Scholar * van Kooten, C. _et al_. B cells regulate expression of CD40 ligand on activated T cells by lowering the mRNA level and through the
release of soluble CD40. _Eur. J. Immunol._ 24, 787–792 (1994). Article CAS Google Scholar * Grammer, A.C. _et al_. The CD40 ligand expressed by human B cells costimulates B Cell
responses. _J. Immunol._ 154, 4996–5010 (1995). CAS PubMed Google Scholar * Yellin, M.J. _et al_. CD40 molecules induce down-modulation and endocytosis of T cell surface T cell-B cell
activating molecule/CD40-L. Potential role in regulating helper effector function. _J. Immunol._ 152, 598–608 (1994). CAS PubMed Google Scholar * Storrie, B. & Edelson, P.J.
Distribution of concanavalin A in fibroblasts: Direct endocytosis versus surface capping. _Cell_ 11, 707–717 (1977). Article CAS Google Scholar * Salisbury, J.L., Condeelis, J.S. &
Satir, P. Role of coated vesicles, microfilaments and calmodulin in receptor-mediated endocytosis by cultured B lymphoblastoid cells. _J. Cell Biol._ 87, 132–141 (1980). Article CAS Google
Scholar * Ranheim, E.A. & Kipps, T.J. Activated T cells induce expression of B7/BB1 on normal or leukemic B cells through a CD40-dependent signal. _J. Exp. Med._ 177, 925–935 (1993).
Article CAS Google Scholar * Notarangelo, L.D., Duse, M. & Ugazio, A.G. Immunodeficiency with hyper-IgM (HIM). _Immunodefic. Rev._ 3, 101–121 (1992). CAS PubMed Google Scholar *
Rossi, E. _et al_. Zeta chain and CD28 are poorly expressed on T lymphocytes from chronic lymphocytic leukemia. _Leukemia_ 10, 494–497 (1996). CAS PubMed Google Scholar * Mizoguchi, H.
_et al_. Alterations in signal transduction molecules in T lymphocytes from tumor-bearing mice. _Science_ 258, 1795–1798 (1992). Article CAS Google Scholar * Bowen, F., Haluskey, J. &
Quill, H. Altered CD40 ligand induction in tolerant T lymphocytes. _Eur. J. Immunol._ 25, 2830–2834 (1995). Article CAS Google Scholar * Hermann, P. _et al_. Expression of a 32-kDa
ligand for the CD40 antigen on activated human T lymphocytes. _Eur. J. Immunol._ 23, 961–964 (1993). Article CAS Google Scholar * Paulie, S. _et al_. A p50 surface antigen restricted to
human urinary bladder carcinomas and B lymphocytes. _Cancer Immunol. Immunother._ 20, 23–28 (1985). Article CAS Google Scholar * Ben-Aissa, H. _et al_. Human bladder cancer associated
antigens: evaluation of antigenicity in TCC tissues of different grades and in normal urothelium. _Anticancer. Res._ 8, 443–449 (1988). CAS PubMed Google Scholar * Hutchins, D. &
Steel, C.M. Regulation of ICAM-1 (CD54) expression in human breast cancer cell lines by interleukin 6 and fibroblast-derived factors. _Int. J. Cancer_ 58, 80–84 (1994). Article CAS Google
Scholar * Pammer, J. _et al_. CD40 antigen is expressed by endotheliai cells and tumor cells in Kaposi's sarcoma. _Am. J. Pathol._ 148, 1387–1396 (1996). CAS PubMed PubMed Central
Google Scholar * Borrow, P. _et al_. CD40L-deficient mice show deficits in antiviral immunity and have an impaired memory CD8+ CTL response. _J. Exp. Med._ 183, 2129–2142 (1996). Article
CAS Google Scholar * Stuber, E., Strober, W. & Neurath, M. Blocking the CD40L-CD40 interaction in vivo specifically prevents the priming of T helper 1 cells through the inhibition of
interleukin 12 secretion. _J. Exp. Med._ 183, 693–698 (1996). Article CAS Google Scholar Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Division of Hematology/Oncology,
Department of Medicine, UCSD School of Medicine, 9500 Gilman Drive, La Jolla, California, 92093-0663, USA Mark Cantwell, Tinh Hua, Jim Pappas & Thomas J. Kipps Authors * Mark Cantwell
View author publications You can also search for this author inPubMed Google Scholar * Tinh Hua View author publications You can also search for this author inPubMed Google Scholar * Jim
Pappas View author publications You can also search for this author inPubMed Google Scholar * Thomas J. Kipps View author publications You can also search for this author inPubMed Google
Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Cantwell, M., Hua, T., Pappas, J. _et al._ Acquired CD40-ligand deficiency in chronic lymphocytic
leukemia. _Nat Med_ 3, 984–989 (1997). https://doi.org/10.1038/nm0997-984 Download citation * Received: 07 January 1997 * Accepted: 18 June 1997 * Issue Date: 01 September 1997 * DOI:
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