Important note: Information in this article was accurate in 1993. The state of the art may have changed since the publication date.
Longitudinal evaluation of immune dysfunction in SIV-infected rhesus macaques, monitored by a novel tri-parametric immunological staging system.
Symp Nonhum Primate Models AIDS. 1992 Nov 17-20;10:abstract no. 100. Unique Identifier : AIDSLINE PRIM10/93200945 Lavergne JA; Del Llano AM; Amieiro JP; Kraiselburd EN; Kessler MJ; Malaga C; Department of Microbiology, University of Puerto Rico, San Juan; 00936-5067.
Abstract:
A novel immunological staging system (ISS) based on three in vitro parameters of immune function (blood cell apoptosis, mitochondrial metabolism and proliferative response to PWM) was utilized for the longitudinal follow-up of a group of eight SIV-infected rhesus macaques, during fifteen months after their infection with SIVsm/E660 (10(-1) to 10(-6) dilutions of 10(4.8) TCID 50/ml). This system allowed the classification of these animals into stages 0, 1, 2 and 3, according to the number of affected parameters, along the progression of their SIV infection. Animals were also monitored monthly for their absolute numbers of blood CD4 lymphocytes, viremia, antibodies to SIV, and for the in vitro production of the cytokines TNF alpha and IL-6. After eight months of infection, none of the experimental animals presented serious immunological dysfunction (none were in stage 3), while most of them were in stages 0 and 1. Between 9 and 11 months post-infection, SIV-infected animals started to become impaired in one or more of their immunological parameters, thus progressing into more advanced stages of the ISS. At the end of month 15 post-infection, when all animals were euthanized, five of the eight macaques were in stage 3, while the remaining three were in stage 2. Interestingly, these last three animals had remained in stage 0 for the first 12 months of the study, progressing into stages 1 and 2 only after 13-15 months of infection. Importantly, the three uninfected control animals remained in stage 0 throughout the duration of this study. The following table summarizes the numbers of SIV-infected macaques progressing through the various stages for the ISS during months 11 to 15 post-infection: TABULAR DATA, SEE ABSTRACT VOLUME. Of the eight macaques in the study only one showed absolute numbers of blood CD4 cells below 200 per cu mm of blood; this particular animal had progressed into stage 3 twelve months after infection with SIV. In addition, the ISS here utilized detected changes in the immune functions of experimental animals before any other physical, clinical or hematological changes appeared, thus supporting its utility in the longitudinal monitoring of SIV infection. This system also proved predictive of disease severity as shown by its correlation with pathological findings at the time of necropsy of the SIV-infected macaques.
Keywords: Animal Antigens, CD4/ANALYSIS Apoptosis Longitudinal Studies Lymphocyte Transformation Lymphocytes/*IMMUNOLOGY/METABOLISM/PHYSIOLOGY Macaca mulatta Mitochondria/METABOLISM Pokeweed Mitogens Simian Acquired Immunodeficiency Syndrome/BLOOD/*IMMUNOLOGY/ PHYSIOPATHOLOGY Support, U.S. Gov't, P.H.S. *SIV Time Factors ABSTRACT 930630
M9361075
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