Important note: Information in this article was accurate in 1986. The state of the art may have changed since the publication date.
CYTOTOXIC CELLULAR IMMUNITY AND CYTOMEGALOVIRUS: LESSONS FROM STUDIES OF THE ACQUIRED IMMUNODEFICIENCY SYNDROME AND IMMUNOSUPPRESSED ALLOGRAFT RECIPIENTS
Prog Leukocyte Biol; 1:159-76 1985. Unique Identifier : AIDSLINE ICDB/86620622 Rook AH; Fauci AS; Lab. of Immunoregulation, Natl. Inst. of Allergy and Infectious; Diseases, NIH, Bethesda, MD 20205
Abstract:
The authors' studies of the effects of cytomegalovirus (CMV) on cytotoxic cellular immunity (CCI) in the acquired immunodeficiency syndrome (AIDS) and immunosuppressed allograft recipients are reviewed. Cytotoxicity assays have shown that specific CMV cytotoxicity occurs early in infection, is greatest against HLA-matched cells, and is mediated by natural killer (NK) cells and antibody-dependent killer cells (ADK). In recipients of marrow or renal transplants, survival after CMV infection corresponds to the levels of CMV-specific cytotoxic T cells and NK cells in the peripheral blood. In a study of 20 renal allograft recipients, allograft dysfunction occurred less frequently in patients (pts) with CMV-specific cytotoxicity than in those without. Active CMV infection is very common in AIDS and can be manifested by pneumonitis, retinitis, ulcerative gastrointestinal lesion, necrosing adrenalitis and encephalitis. Most AIDS pts have decreased CMV-specific cytotoxicity and many also exhibit depressed NK activity. The peripheral blood monocytes of AIDS pts also have decreased ability to produce the lymphokines interleukin-2 (IL-2) and gamma-interferon (IFN). Preliminary evidence suggests that in vitro infection of mononuclear cells by CMV depresses monocyte antigen presentation, reduces the release of IL-1 and gamma-IFN, and completely inhibits NK activity. In vitro studies of NK cells from marrow allograft recipients have shown that beta-IFN promotes NK activity early, but not late, in the course of CMV infection. NK cells and CMV-specific cytotoxicity in marrow allograft recipients are also highly responsive to IL-2. In contrast to lymphocytes of marrow graft recipients, lymphocytes from AIDS pts respond to IL-2 but not to exogenous alpha- or beta-IFN; therapeutic use of IL-2 in AIDS has resulted in some immunologic changes but no clinical benefit. Lymphocyte transfer and marrow transplantation from a healthy identical twin to his sibling with AIDS resulted in a transient improvement in the pt's immune function. The authors conclude that CCI is preeminent in recovery from CMV infection but that numerous other immunological factors are probably contributory. (27 Refs)
Keywords: Acquired Immunodeficiency Syndrome/*IMMUNOLOGY Bone Marrow/TRANSPLANTATION Bone Marrow Transplantation Cytomegalovirus/IMMUNOLOGY Cytomegalovirus Infections/*IMMUNOLOGY/THERAPY Cytotoxicity, Immunologic Histocompatibility Testing Human *Immune Tolerance Immunity, Cellular Interferon Type I/THERAPEUTIC USE Interferon Type II/THERAPEUTIC USE Interleukin-2/ADMINISTRATION & DOSAGE Kidney/TRANSPLANTATION Kidney Transplantation Killer Cells, Natural/IMMUNOLOGY Lymphocyte Transformation T-Lymphocytes, Cytotoxic/IMMUNOLOGY *Transplantation Immunology MEETING PAPER
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Important note: Information in this article was accurate in 1986. The state of the art may have changed since the publication date.
