Immune activation in the context of HIV infection

• Published in: Clinical and experimental immunology Vol. 111; no. 1; pp. 1 - 2
• Main Authors: Bentwich, Z, Kalinkovich, A, Weisman, Z, Grossman, Z
• Format: Journal Article
• Language: English
• Published: Oxford BSL Blackwell Science Ltd 01.01.1998; Blackwell Science Inc
• Subjects: HIV Infections - immunology; Humans; Immunity
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1046/j.1365-2249.1998.00483.x

In the article by Vingerhoets et al., published in this issue, the reasons for the defective response of T cells obtained from HIV-infected patients to stimulation by superantigens have been explored. The authors describe a marked diminution in response of both T cell subsets during HIV infection that appears first in CD8 cells, is related to the progression of the disease, and is associated with increased levels of apoptosis. They ascribe these changes to extrinsic and intrinsic cellular defects, and rightly point out that several non-exclusive mechanisms could explain T cell dysfunction in the course of HIV infection. In concluding their article, the authors are still not clear as to the direct causes of the impaired responses they have described, and indicate that further studies are needed to identify and characterize these defects and the molecular regulation of apoptosis. However, beyond the questions of molecular mechanisms, there are conceptual issues regarding the nature of chronic infection and possible adaptive value of the functional modifications observed versus their pathogenic significance. Persistent activation of the immune system is one of the hallmarks of HIV infection. Already in 1983, Shearer compared this activation to that occurring in graft versus host reaction. Others have pointed to the role of immune activation in enhancement of viral replication and dissemination, thereby affecting progression of the disease. Ascher & Sheppard proposed, several years ago, that abnormal non-specific activation of CD4 T cells by the virus is responsible for a dysregulation of their turnover and for the development of immunodeficiency. We have proposed more recently that chronic immune activation caused by chronic infections is a major factor in the pathogenesis of AIDS in Africa, by making the host more susceptible to HIV infection and less able to cope with it once infected. We have also proposed that persistent stimulation of the immune system by HIV infection, in itself, is sufficient to cause most if not all of the numerical, phenotypic and functional changes that are observed. Progression of the disease was attributed to the persistent `stress', resulting in an ageing-like process of the immune system in terms of the functional phenotype. These ideas challenged the generally accepted view that HIV `depletes' the CD4 lymphocyte pool by effecting the killing of these cells, directly or indirectly. Specifically, we have proposed that two major processes are responsible for the diminution of CD4 T cell counts in blood during the asymptomatic phase of the disease: (i) activation-associated redistribution of T cells between the blood compartment and the lymphoid tissues; and (ii) activation-associated attenuation of the proliferation of CD4 T cells in the infected tissues. Redistribution may be related to changes in expression of cell surface molecules on activated cells and consequently in cell migration patterns. Indeed, there is now evidence supporting the view that the diminution of CD4 cell numbers in blood does not reflect comparable depletion in lymphoid tissue.