CD8+ T cell subsets of cytotoxic T lymphocytes induced by Epstein-Barr virus infection in infectious mononucleosis.

Abstract

Mononuclear peripheral blood lymphocytes (PBL) from patient with infectious mononucleosis (IM) were tested in a 51Cr-release assay for cytotoxicity against autologous and allogeneic lymphoblastoid cell line (LCL), or Epstein-Barr virus (EBV)-genome positive and negative cell line. In acute phase, PBL lyse an autologous LCL as well as allogeneic LCL (Wa cells). High levels of cytotoxicity were observed in the combinations between effector and target cells sharing HLA-Class 1 product. EBV-genome positive Daudi and Raji cells which lack HLA-Class 1 antigen and have mismactched HLA-Class 1 antigen, respectively showed resistance to killing. EBV-genome negative tumor cells except NK sensitive K562 cells were not killed by IM lymphocytes. However, the IM lymphocytes without atypical form in convalescent phase failed to show killing activity against autologous and allogeneic LCL. These findings suggest that cell surface membrane antigen structure on EBV-infected LCL may be able to explain the recognition and triggering of lysis of target cells by HLA-Class 1 restricted cytotoxic T cells (CTL) from acute IM. Phenotypic analysis of PBL with atypical form from IM was made by two-color flow cytometry. The data demonstrate that CD8+ T cells quantitatively represent the major population of lymphocytes expanded during acute IM. Furthermore, approximately 70% of these CD8+ T cells express HLA-DR on these surface, suggesting that they have undergone activation. However, IL 2R (CD25 antigen) expression was not significantly elevated on activated T cells. The salient profile on cytofluorographs of an acute IM was the increased number of CD3+CD19-, CD8+CDllb-, CD8+CD28+ and CD8+S6F1+ cells. However, CD3-CD19+, CD8+CDllb+, CD8+S6F1-, CD4+Leu8-and CD25+HLA-DW antigens were little expressed. Increased number of CD8~CDllb-, CD8+CD28+ and CD8+ S6F1+ cells, which are regarded as CTL were reduced according to the improvement of the clinical symptoms and laboratory findings. These results together with HLA typing analysis suggested a possibility HLA-Class 1 restriction of the CTL with surface phenotype of CD8+CDllb-, CD8+CD28+, and CD8+S6F1t cytotoxic T cells (CTL) ; CD8 T cells ; HLA ; Epstein-Barr virus

Detection of Influenza Virus Induced Ultrastructural Changes and DNA Damage

“…), washed in PBS and fixed with Karnovsky's fixative (4% paraformaldehyde and 1% glutaraldehyde) overnight. The fixed cells were then submitted for Transmission Electron Microscopy (TEM) to the All India Institute of Medical Sciences, at the Department of Electron Microscopy, and a detailed study of the ultra structural changes occurring during influenza A virus infection was conducted [27]. …”

Immune dysregulation and CD4+ T cell loss in HIV-1 infection

“…Although it was argued by Estaquier et al [47] that CD4 + cell death is specific for HIV infection, in Epstein-Barr virus (EBV) infection in humans, both CD4 + and CD8 + cells also die upon culture [106,149]. Dying cells were confined to the CD45RO + population and cell death could be prevented by culture in the presence of cytokines such as interleukin (IL)-2 [12,149]. Under these conditions, it was suggested that PCD affects the population of activated T cells that expands during the acute phase of the infection.…”

“…The apoptosis-related Fas antigen is known to be preferentially expressed on previously activated or memory T cells [104]. Fas-Fas ligand (FasL) interaction might play a role by the elimination of excessive immune cells, since CD45RO + cells in acute EBV infection, known to undergo apoptosis, have increased expression of Fas [149]. In HlV-infected individuals, T cells also have an increased expression of Fas and increased percentages of cells dying in culture upon Fas ligation with anti-Fas antibodies [70].…”

Selective CD4+ T cell deletion after specific activation in HIV-infected individuals; protection by anti-CD28 monoclonal antibodies

“…This spontaneous cell death reflects in fact the continuous activation of the cells in vivo [11,12]. It affects primarily CD8 T cells [13][14][15], and has already been described for different acute or chronic viral pathologies like lymphocytic choriomeningitis virus infection in mice [16] or Epstein-Barr virus (EBV) infection in humans [17,18]. It does not correlate with the stage of the disease [11,12,14,15], nor is it specific for AIDS [8].…”

“…One, involving mainly CD8 T cells, could be an indirect consequence of immune activation that occurs during both pathogenic and non-pathogenic lentiviral infections, as well as in other circumstances [16][17][18]; the other, involving CD4 T cells, seems closely related to AIDS physiopathology and can more probably explain the specific deletion of these cells observed in vivo. It was therefore important to analyse further this AICD mechanism in HIV-infected individuals to determine the specificity of the induction of apoptosis after TCR mobilization, and the number of specific T cells that undergo apoptosis.…”