IS CHRONIC IMMUNE ACTIVATION ALONE ENOUGH TO INDUCE CD4+ T CELL LOSS?

To study if chronic immune activation could induce CD4⁺ T cell loss directly, Tesselaar et al. studied T cell dynamics in other situations of chronic immune stimulation independent of HIV infection.⁸⁵ A transgenic mouse model was developed in which CD70 is constitutively expressed on the cell surface of B cells.

A similar HIV-independent disturbance of the T cell pool reminiscent of HIV infection was observed in a large group of healthy Ethiopians analyzed in the Ethio-Netherlands AIDS Research Project (ENARP). HIV-negative Ethiopians were found to have highly increased levels of immune activation compared to HIV-negative Dutch individuals, probably related to differences in domestic antigen exposure and the high antigenic burden by common parasitic infections in Ethiopia.⁸⁶,⁸⁷ In fact, these healthy individuals have low CD4⁺ T cell counts, low percentages of CD4⁺ and CD8⁺ naive T cells, expansion of CD8⁺ memory and effector T cell subsets, and decreased TREC contents, comparable to HIV-infected Dutch individuals.⁵¹,⁸⁶,⁸⁷ Changes in the peripheral T cell pool of healthy Ethiopians appeared to occur at very early ages. Whereas cord blood samples from healthy Ethi­opians and Dutch individuals were virtually identical with respect to TREC contents and T cell subsets, within a few years of childhood, considerable differences were observed (Tsegaye et al., submitted).⁸⁸ Thus, also in this situation, chronic antigen exposure and chronically increased immune activation were associated with progressive CD4⁺ T cell decline.

The fact that a considerable T cell loss can be observed in situations of chronic immune activation independent of HIV infection suggests that CD4⁺ T cell loss in HIV infection may be a direct result of chronic stimulation induced by HIV. Of note, even in healthy individuals, the total number of T cells, including the number of naive CD4⁺ and CD8⁺ T cells, declines with increasing age.⁸9,9⁰