The combined assessment of cellular apoptosis, mitochondrial function and proliferative response to PWM has predictive value in SIV infection.

Important note: Information in this article was accurate in 1993. The state of the art may have changed since the publication date.

The combined assessment of cellular apoptosis, mitochondrial function and proliferative response to PWM has predictive value in SIV infection.

Symp Nonhum Primate Models AIDS. 1992 Nov 17-20;10:abstract no. 13. Unique Identifier : AIDSLINE PRIM10/93200976
Del Llano AM; Lavergne JA; Department of Microbiology, University of Puerto Rico, San Juan; 00936-5067.

Abstract: Routine monitoring of SIV-infected macaques includes the assessment of clinical parameters of disease progression, such as persistent lymphadenopathy, diarrhoea or weight loss. However, these clinical signs usually become evident only after significant immunologic impairment has already occurred in the animal. The need for the development of early markers of disease progression, which correlate with the later appearance of viral antigenemia and depletion of blood CD4 lymphocytes, is therefore evident. This work describes a new approach to the prognostic evaluation of SIV infection, utilizing a three-parametric functional assessment of peripheral blood mononuclear cells from SIV-infected macaques. This tri-functional in vitro evaluation allows for the classification of infected animals in convenient stages, according to the number of in vitro parameters affected. The classifying parameters used are: the mitochondrial metabolic activity of freshly isolated blood mononuclear cells (BMNC), measured by an MTT-reduction assay; the detection of apoptosis in 72 hour cultures of BMNC, assessed by propidium iodide staining and dual-parametric flow cytometric analysis; and the proliferative response, measured by flow cytometry, of BMNC to pokeweed mitogen (PWM), an established correlate of immune function in HIV/SIV infection. Results obtained from sequential assays performed by us at monthly intervals during a period of several months, indicate that the BMNC from SIV-infected macaques may present one or more of the following in vitro characteristics: 1) an impairment in their mitochondrial dehydrogenase activity; 2) development of various degrees of apoptosis when cultured for 72 hours and then examined for their nuclear granularity and DNA content (A0 zone) by flow cytometry and 3) a poor proliferative response to the mitogen PWM. Thus, the combination of observed parametric results among individual animals has allowed us to develop a versatile staging system with prognostic value in SIV-infection. Based on these observations, experimental animals have been classified in four stages: Stage 0, which includes uninfected controls and all other animals with unaffected parameters; Stage 1, with animals having only one parameter affected; and Stages 2 and 3, which include animals presenting two or all three parameters affected, respectively. This type of three-parametric evaluation of SIV-infected macaques has proven to be a predictive tool in the longitudinal follow-up of these animals, by demonstrating the irreversible progression of infected macaques from Stage 0 during early infection, to stages 1, 2 or 3 during later infection phases. In addition, the animal progression through stages 0 to 3 may take place even before CD4 cell depletion occurs, indicating its early prognostic value in SIV disease.

Keywords: Animal *Apoptosis Cells, Cultured Flow Cytometry *Lymphocyte Transformation Lymphocytes/IMMUNOLOGY/METABOLISM/*PHYSIOLOGY Macaca Mitochondria/*METABOLISM Pokeweed Mitogens Prognosis Simian Acquired Immunodeficiency Syndrome/IMMUNOLOGY/METABOLISM/ *PHYSIOPATHOLOGY Support, U.S. Gov't, P.H.S. *SIV Time Factors ABSTRACT
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