CD8hi+CD57+ T lymphocytes are enriched in antigen-specific T cells capable of down-modulating cytotoxic activity.

Major expansions of CD8hi+CD57+ T lymphocytes frequently occur during human immunodeficiency virus (HIV) infection and after transplantation. To investigate mechanisms of such cell expansion, we compared the activation and functional status of CD8hi+CD57+ and CD57-peripheral blood lymphocytes (PBL) from normal, bone marrow transplantation (BMT) and HIV+ donors. The CD8hi+CD57+ PBL from BMT and HIV+ donors preferentially displayed CD38 and HLA-DR activation markers without correlation between CD8hi+CD57+ percentages and HIV load, the CD45RA+ isoform in all ex vivo conditions but acquired CD45RO after in vitro expansion, CD11b and CD11c in BMT and HIV+ donors but decreased expression of CD62-L, VLA-2 and VLA-6. The CD8hi+CD57+ cells were positive for perforin and granzyme B and spontaneously mediated cytolytic activity in a CD3-redirected assay. In contrast the inhibitor of cytolytic functions (ICF) produced by CD8hi+CD57+ cells down-modulated the CD3-redirected cytolytic activity but only at low levels of CD3 cross-linking. While CD3-triggering induced a low, if any, short-term proliferation of CD8+CD57+ cells, this subset could be amplified after long-term stimulation either with mitogens or with HIV antigens, thereby enriched in HIV-specific T cells producing tumor necrosis factor-alpha. Altogether these data suggest that CD8hi+CD57+ cells represent a terminal differentiation state of activated effector cytotoxic T lymphocytes which are enriched in antigen-specific T cells and down-modulate their own cytolytic potential, thus participating in a negative control of effector cell functions during persistent viral infections or transplantations.

[1]  J Leibowitch,et al.  Positive effects of combined antiretroviral therapy on CD4+ T cell homeostasis and function in advanced HIV disease. , 1997, Science.

[2]  Niels Schaft,et al.  T Cell Telomere Length in HIV-1 Infection: No Evidence for Increased CD4+ T Cell Turnover , 1996, Science.

[3]  G S Kansas,et al.  Selectins and their ligands: current concepts and controversies. , 1996, Blood.

[4]  Philip J. R. Goulder,et al.  Phenotypic Analysis of Antigen-Specific T Lymphocytes , 1996, Science.

[5]  Antonio Lanzavecchia,et al.  T Cell Activation Determined by T Cell Receptor Number and Tunable Thresholds , 1996, Science.

[6]  C. Harley,et al.  Shortened telomeres in the expanded CD28-CD8+ cell subset in HIV disease implicate replicative senescence in HIV pathogenesis. , 1996, AIDS.

[7]  Rolf M. Zinkernagel,et al.  Immunology Taught by Viruses , 1996, Science.

[8]  R. Zinkernagel,et al.  The roles of perforin‐ and Fas‐dependent cytotoxicity in protection against cytopathic and noncytopathic viruses , 1995, European journal of immunology.

[9]  P. Lehner,et al.  CD8highCD57+ T lymphocytes in normal, healthy individuals are oligoclonal and respond to human cytomegalovirus. , 1995, Journal of immunology.

[10]  J. Ceuppens,et al.  Increased cytolytic T lymphocyte activity and decreased B7 responsiveness are associated with CD28 down‐regulation on CD8+ T cells from HIV‐infected subjects , 1995, Clinical and experimental immunology.

[11]  R. Rabin,et al.  Altered representation of naive and memory CD8 T cell subsets in HIV-infected children. , 1995, The Journal of clinical investigation.

[12]  B. Autran,et al.  Expansion of CD4+CD7- T helper cells with a TH0-TH2 function in kidney transplant recipients. , 1995, Transplantation proceedings.

[13]  S. Ferrini,et al.  Cytolytic T lymphocytes displaying natural killer (NK)-like activity: expression of NK-related functional receptors for HLA class I molecules (p58 and CD94) and inhibitory effect on the TCR-mediated target cell lysis or lymphokine production. , 1995, International immunology.

[14]  K. Baetz,et al.  Serial killing by cytotoxic T lymphocytes: T cell receptor triggers degranulation, re‐filling of the lytic granules and secretion of lytic proteins via a non‐granule pathway , 1995, European journal of immunology.

[15]  R. Seder,et al.  The functional role of CD8+ T helper type 2 cells , 1995, The Journal of experimental medicine.

[16]  B. Autran,et al.  An inhibitor of cytotoxic functions produced by CD8+CD57+ T lymphocytes from patients suffering from AIDS and immunosuppressed bone marrow recipients , 1994, European journal of immunology.

[17]  Persephone Borrow,et al.  Major expansion of CD8+ T cells with a predominant Vβ usage during the primary immune response to HIV , 1994, Nature.

[18]  H Hengartner,et al.  Fas and perforin pathways as major mechanisms of T cell-mediated cytotoxicity. , 1994, Science.

[19]  T. Rème,et al.  CD57+ T lymphocytes are derived from CD57− precursors by differentiation occurring in late immune responses , 1994, European journal of immunology.

[20]  R. Lechler,et al.  Anergic T cells as suppressor cells in vitro. , 1994, Science.

[21]  T. Springer.  Traffic signals for lymphocyte recirculation and leukocyte emigration: The multistep paradigm , 1994, Cell.

[22]  F. Sigaux,et al.  Oligoclonal expansion of CD8+ CD57+ T cells with restricted T-cell receptor beta chain variability after bone marrow transplantation. , 1994, Blood.

[23]  L. Borysiewicz,et al.  Subsets of CD8 +, CD57+ cells in normal, healthy individuals: correlations with human cytomegalovirus (HCMV) carrier status, phenotypic and functional analyses , 1993, Clinical and experimental immunology.

[24]  O. Lantz,et al.  Apoptosis of activated CD8+/CD57+ T cells is induced by some combinations of anti-CD2 mAb. , 1993, Journal of immunology.

[25]  M. Salmon,et al.  The significance of low bcl-2 expression by CD45RO T cells in normal individuals and patients with acute viral infections. The role of apoptosis in T cell memory , 1993, The Journal of experimental medicine.

[26]  P. Allen,et al.  Induction of T-cell anergy by altered T-cell-receptor ligand on live antigen-presenting cells , 1993, Nature.

[27]  B. Walker,et al.  Human immunodeficiency virus type 1-specific cytotoxic T lymphocytes release gamma interferon, tumor necrosis factor alpha (TNF-alpha), and TNF-beta when they encounter their target antigens , 1993, Journal of virology.

[28]  J. Giorgi,et al.  Circulating HIV-specific CD8+ cytotoxic T cells express CD38 and HLA-DR antigens. , 1993, Journal of immunology.

[29]  L. Lanier,et al.  CD28- T lymphocytes. Antigenic and functional properties. , 1993, Journal of immunology.

[30]  H. Matsuda,et al.  Both CD45RA+ and CD45RA- subpopulations of CD8+ T cells contain cells with high levels of lymphocyte function-associated antigen-1 expression, a phenotype of primed T cells. , 1993, Journal of immunology.

[31]  J. Pocidalo,et al.  The significance of activation markers on CD8 lymphocytes in human immunodeficiency syndrome: staging and prognostic value , 1992, Clinical and experimental immunology.

[32]  G. Prud’homme,et al.  IDENTIFICATION OF NATURAL SUPPRESSOR CELLS IN LONG‐TERM RENAL ALLOGRAFT RECIPIENTS , 1992, Transplantation.

[33]  Richard O. Hynes,et al.  Integrins: Versatility, modulation, and signaling in cell adhesion , 1992, Cell.

[34]  C. Katlama,et al.  CD4+CD7-CD57+ T cells: a new T-lymphocyte subset expanded during human immunodeficiency virus infection. , 1992, Blood.

[35]  G. Inghirami,et al.  The kinetics and temporal expression of T-cell activation-associated antigens CD15 (LeuM1), CD30 (Ki-1), EMA, and CD11c (LeuM5) by benign activated T cells. , 1992, Hematologic pathology.

[36]  Y. Tanaka,et al.  Lymphocyte interactions with endothelial cells. , 1992, Immunology today.

[37]  B. Walker,et al.  An optimal viral peptide recognized by CD8+ T cells binds very tightly to the restricting class I major histocompatibility complex protein on intact cells but not to the purified class I protein. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[38]  C. Katlama,et al.  A lectin‐binding soluble factor released by CD8+CD57+ lymphocytes from AIDS patients inhibits T cell cytotoxicity , 1991, European journal of immunology.

[39]  E. Bell,et al.  Interconversion of CD45R subsets of CD4 T cells in vivo , 1990, Nature.

[40]  Timothy A. Springer,et al.  Adhesion receptors of the immune system , 1990, Nature.

[41]  K. Horgan,et al.  Regulated expression and binding of three VLA (β1) integrin receptors on T cells , 1990, Nature.

[42]  M. Hemler.  VLA proteins in the integrin family: structures, functions, and their role on leukocytes. , 1990, Annual review of immunology.

[43]  B. Autran,et al.  Cell-mediated suppression of HIV-specific cytotoxic T lymphocytes. , 1989, Journal of immunology.

[44]  R. Detels,et al.  T-cell subset alterations in HIV-infected homosexual men: NIAID Multicenter AIDS cohort study. , 1989, Clinical immunology and immunopathology.

[45]  S. James,et al.  Role of CD2 in activation and cytotoxic function of CD8/Leu-7-positive T cells. , 1988, Journal of immunology.

[46]  J. Farcet,et al.  Persistence of T8+/HNK-1+ suppressor lymphocytes in the blood of long-term surviving patients after allogeneic bone marrow transplantation. , 1986, Journal of immunology.

[47]  L. Lanier,et al.  Lectin-dependent and anti-CD3 induced cytotoxicity are preferentially mediated by peripheral blood cytotoxic T lymphocytes expressing Leu-7 antigen. , 1986, Journal of immunology.

[48]  D. Spiegelhalter,et al.  Cytomegalovirus infection in cardiac transplant recipients associated with chronic T cell subset ratio inversion with expansion of a Leu-7+ TS-C+ subset. , 1985, Clinical and Experimental Immunology.

[49]  A. Gratwohl,et al.  The effect of cytomegalovirus infection on T lymphocytes after allogeneic bone marrow transplantation. , 1985, Clinical and experimental immunology.

[50]  J. Fahey,et al.  Reduced ecto-5'-nucleotidase activity and enhanced OKT10 and HLA-DR expression on CD8 (T suppressor/cytotoxic) lymphocytes in the acquired immune deficiency syndrome: evidence of CD8 cell immaturity. , 1985, Journal of immunology.

[51]  R. Guttmann,et al.  HNK-1+ (Leu-7) and other lymphocyte subsets in long-term survivors with renal allotransplants. , 1985, Transplantation.

[52]  C. Grossi,et al.  Morphologic and phenotypic features of the subpopulation of Leu-2+ cells that suppresses B cell differentiation. , 1984, Journal of immunology.

[53]  L. Lanier,et al.  Human lymphocyte subpopulations identified by using three-color immunofluorescence and flow cytometry analysis: correlation of Leu-2, Leu-3, Leu-7, Leu-8, and Leu-11 cell surface antigen expression. , 1984, Journal of immunology.

[54]  A. Landay,et al.  Characterization of a phenotypically distinct subpopulation of Leu-2+ cells that suppresses T cell proliferative responses. , 1983, Journal of immunology.

[55]  C. Balch,et al.  A differentiation antigen of human NK and K cells identified by a monoclonal antibody (HNK-1). , 1981, Journal of immunology.

[56]  E Niskanen,et al.  MARROW TRANSPLANTATION , 1977, Duodecim; laaketieteellinen aikakauskirja.