HIV-induced decline in blood CD4/CD8 ratios: viral killing or altered lymphocyte trafficking?

Abstract During HIV infection, CD4 + -cell numbers and CD4/CD8 ratios decline in the blood. This is usually attributed to direct viral killing or to other indirect mechanisms. However, current models generally assume that such changes in the blood are representative of changes in total CD4 + -cell numbers throughout the body. This article discusses the importance of alterations in CD4 + - and CD8 + -cell migration in regulating blood lymphocyte levels and questions the extent of virus-mediated CD4 + -cell destruction.

[1]  A. Cafaro,et al.  Characteristics of the CD8+ lymphocytosis during primary simian immunodeficiency virus infections , 1997, AIDS.

[2]  N. Brousse,et al.  Production of interleukins in human immunodeficiency virus-1-replicating lymph nodes. , 1990, The Journal of clinical investigation.

[3]  Z. Grossman,et al.  From HIV infection to AIDS: are the manifestations of effective immune resistance misinterpreted? , 1993, Clinical immunology and immunopathology.

[4]  C. Fox,et al.  Lymphoid germinal centers are reservoirs of human immunodeficiency virus type 1 RNA. , 1991, The Journal of infectious diseases.

[5]  M. Johnson,et al.  Lymphocyte activation in HIV‐1 infection. II. Functional defects of CD28− T cells , 1994, AIDS.

[6]  N. Letvin,et al.  An activated CD8+ lymphocyte appears in lymph nodes of rhesus monkeys early after infection with simian immunodeficiency virus. , 1991, The Journal of clinical investigation.

[7]  H. Prince,et al.  HIV-related alterations in CD8 cell subsets defined by in vitro survival characteristics. , 1991, Cellular immunology.

[8]  S. Arya,et al.  Identification of RANTES, MIP-1α, and MIP-1β as the Major HIV-Suppressive Factors Produced by CD8+ T Cells , 1995, Science.

[9]  D. Wakefield,et al.  Chemokines and T lymphocyte recruitment to lymph nodes in HIV infection. , 1996, The American journal of pathology.

[10]  J. Sprent,et al.  Induction of Bystander T Cell Proliferation by Viruses and Type I Interferon in Vivo , 1996, Science.

[11]  S. Shaw,et al.  T cell adhesion to endothelium: the FRC conduit system and other anatomic and molecular features which facilitate the adhesion cascade in lymph node. , 1993, Seminars in immunology.

[12]  G. Janossy,et al.  An immunohistological approach to persistent lymphadenopathy and its relevance to AIDS. , 1985, Clinical and experimental immunology.

[13]  G. Eddy,et al.  Immunological and virological changes associated with decline in CD4/CD8 ratios in lymphoid organs of SIV-infected macaques. , 1994, AIDS research and human retroviruses.

[14]  M. Zaccolo,et al.  Involvement of the multilineage CD38 molecule in a unique pathway of cell activation and proliferation. , 1990, Journal of immunology.

[15]  T. Curiel,et al.  Apoptosis occurs predominantly in bystander cells and not in productively infected cells of HIV- and SIV-infected lymph nodes , 1995, Nature Medicine.

[16]  E. Kaldjian,et al.  Orchestrated information transfer underlying leukocyte endothelial interactions. , 1996, Annual review of immunology.

[17]  L. Picker,et al.  Lymphocyte Homing and Homeostasis , 1996, Science.

[18]  M. Cloyd,et al.  HIV induces homing of resting T lymphocytes to lymph nodes. , 1997, Virology.

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

[20]  A. Perelson,et al.  Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection , 1995, Nature.

[21]  L. Montagnier,et al.  Programmed cell death in peripheral lymphocytes from HIV-infected persons: increased susceptibility to apoptosis of CD4 and CD8 T cells correlates with lymphocyte activation and with disease progression. , 1996, Journal of immunology.

[22]  G. Danieli,et al.  Genetic control of the CD4/CD8 T-cell ratio in humans , 1995, Nature Medicine.

[23]  D. Cooper,et al.  Alterations in the immune response of human immunodeficiency virus (HIV)-infected subjects treated with an HIV-specific protease inhibitor, ritonavir. , 1996, The Journal of infectious diseases.

[24]  M. Roederer,et al.  Changes in antigen densities on leukocyte subsets correlate with progression of HIV disease. , 1996, International immunology.

[25]  G. Eddy,et al.  Decline in the CD4+ lymphocyte population in the blood of SIV-infected macaques is not reflected in lymph nodes. , 1993, AIDS research and human retroviruses.

[26]  R. Steinman,et al.  Dendritic cell-T cell conjugates that migrate from normal human skin are an explosive site of infection for HIV-1. , 1995, Advances in experimental medicine and biology.

[27]  H. Schuitemaker,et al.  Viro‐immunological studies in acute HIV‐1 infection , 1994, AIDS.

[28]  G. Bokoch,et al.  Sophisticated strategies for information encounter in the lymph node: the reticular network as a conduit of soluble information and a highway for cell traffic. , 1996, Journal of immunology.

[29]  Christine A. Lee,et al.  Presence of CD3+CD8+Bcl-2(low) lymphocytes undergoing apoptosis and activated macrophages in lymph nodes of HIV-1+ patients. , 1995, The American journal of pathology.

[30]  T. Springer,et al.  Traffic signals on endothelium for lymphocyte recirculation and leukocyte emigration. , 1995, Annual review of physiology.

[31]  Alan S. Perelson,et al.  Quantitative Image Analysis of HIV-1 Infection in Lymphoid Tissue , 1996, Science.

[32]  A. Steffan,et al.  Morphological changes in lymph nodes and expression of VCAM1 and cytokines at the late stages of SIV-induced disease in rhesus monkeys. , 1995, Research in virology.

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

[34]  R. Siliciano,et al.  Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection , 1997, Nature.

[35]  M. Wainberg,et al.  Cell surface down‐modulation of CD4 after infection by HIV‐1 , 1994, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[36]  C. Meijer,et al.  Adhesion of human B cells to follicular dendritic cells involves both the lymphocyte function-associated antigen 1/intercellular adhesion molecule 1 and very late antigen 4/vascular cell adhesion molecule 1 pathways , 1991, The Journal of experimental medicine.

[37]  R. Pabst,et al.  Lymphocyte subsets in the blood: a diagnostic window on the lymphoid system? , 1990, Immunology today.

[38]  R. Pabst,et al.  IFN-gamma influences the migration of thoracic duct B and T lymphocyte subsets in vivo. Random increase in disappearance from the blood and differential decrease in reappearance in the lymph. , 1993, Journal of immunology.

[39]  S. Dewhurst,et al.  Apoptosis correlates with immune activation in intestinal lymphoid tissue from macaques acutely infected by a highly enteropathic simian immunodeficiency virus, SIVsmmPBj14. , 1996, Virology.

[40]  K. McKinnon,et al.  Virus-induced cytokines regulate circulating lymphocyte levels during primary SIV infections. , 1997, International immunology.

[41]  M. Dietrich,et al.  Spectrum of morphologic changes of lymph nodes from patients with AIDS or AIDS-related complexes. , 1986, Progress in allergy.