Perforin dependence of natural killer cell‐mediated tumor control in vivo

Adaptive immune surveillance by T cells against infections and tumors depends on the presence of antigenic peptides presented by major histocompatibility complex (MHC) molecules. If antigenic tumor‐specific peptides or MHC class I molecules are absent, the adaptive T cell immune response fails. Natural killer (NK) cells seem to complement the specific T cells by recognizing target cells lacking MHC class I (e.g. RMA‐S). The role of perforin, which is crucially involved in T cell and NK cell‐mediated target cell lysis, was evaluated in mice lacking perforin with respect to their capacity to eliminate a syngeneic lymphoid tumor. Here, we show that growth of MHC class I− RMA‐S tumor cells in unprimed mice was controlled by NK cells through perforin‐dependent cytotoxicity.

[1]  R. Zinkernagel,et al.  Lymphocyte‐mediated Cytotoxicity in vitro and in vivo: Mechanisms and Significance , 1995, Immunological reviews.

[2]  P. A. Peterson,et al.  A viral inhibitor of peptide transporters for antigen presentation , 1995, Nature.

[3]  J. Yewdell,et al.  Herpes simplex virus turns off the TAP to evade host immunity , 1995, Nature.

[4]  Eric O Long,et al.  Molecular clones of the p58 NK cell receptor reveal immunoglobulin-related molecules with diversity in both the extra- and intracellular domains. , 1995, Immunity.

[5]  M. Colonna,et al.  Cloning of immunoglobulin-superfamily members associated with HLA-C and HLA-B recognition by human natural killer cells. , 1995, Science.

[6]  K. Kärre.  Express yourself or die: peptides, MHC molecules, and NK cells. , 1995, Science.

[7]  C. Walsh,et al.  The role of the Fas lytic pathway in a perforin-less CTL hybridoma. , 1994, Journal of immunology.

[8]  J. Tschopp,et al.  Cytolytic T-cell cytotoxicity is mediated through perforin and Fas lytic pathways , 1994, Nature.

[9]  S. Yonehara,et al.  Cytotoxicity of fresh NK1.1+ T cell receptor alpha/beta+ thymocytes against a CD4+8+ thymocyte population associated with intact Fas antigen expression on the target , 1994, The Journal of experimental medicine.

[10]  K. Okumura,et al.  Two distinct pathways of specific killing revealed by perforin mutant cytotoxic T lymphocytes. , 1994, Immunity.

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

[12]  Hans Hengartner,et al.  Cytotoxicity mediated by T cells and natural killer cells is greatly impaired in perforin-deficient mice , 1994, Nature.

[13]  P. Golstein,et al.  Fas involvement in Ca(2+)-independent T cell-mediated cytotoxicity , 1993, The Journal of experimental medicine.

[14]  T. Mak,et al.  CD8 is needed for development of cytotoxic T but not helper T cells , 1991, Cell.

[15]  G. Klein,et al.  Afferent and efferent cellular interactions in natural resistance directed against MHC class I deficient tumor grafts. , 1988, Journal of immunology.

[16]  H. Ljunggren,et al.  Selective rejection of H–2-deficient lymphoma variants suggests alternative immune defence strategy , 1986, Nature.

[17]  S. Segal,et al.  Abrogation of metastatic properties of tumour cells by de novo expression of H–2K antigens following H–2 gene transfection , 1985, Nature.

[18]  H. Ljunggren,et al.  Host resistance directed selectively against H-2-deficient lymphoma variants. Analysis of the mechanism , 1985, The Journal of experimental medicine.

[19]  R. Kiessling,et al.  „Natural”︁ killer cells in the mouse. I. Cytotoxic cells with specificity for mouse Moloney leukemia cells. Specificity and distribution according to genotype , 1975, European journal of immunology.

[20]  P. Bruggen,et al.  Tumor antigens recognized by T lymphocytes. , 1994, Annual review of immunology.

[21]  C. Melief,et al.  Tumor eradication by adoptive transfer of cytotoxic T lymphocytes. , 1992, Advances in cancer research.

[22]  P. Greenberg.  Adoptive T cell therapy of tumors: mechanisms operative in the recognition and elimination of tumor cells. , 1991, Advances in immunology.

[23]  P. Henkart.  Mechanism of lymphocyte-mediated cytotoxicity. , 1985, Annual review of immunology.

[24]  M. Chase.  Immunology and experimental dermatology. , 1985, Annual review of immunology.

[25]  P. Doherty,et al.  Immunological surveillance of tumors in the context of major histocompatibility complex restriction of T cell function. , 1984, Advances in cancer research.

[26]  A. Eb,et al.  Expression of class I major histocompatibility antigens switched off by highly oncogenic adenovirus 12 in transformed rat cells , 1983, Nature.

[27]  C. Melief,et al.  Tumorigenicity of cells transformed by adenovirus type 12 by evasion of T-cell immunity , 1983, Nature.