In their earlier, much quoted, viewpoint article, Mario Clerici and Gene Shearer examined the role of T helper 1 (Th1)- and Th2-type responses in immune dysregulation associated with human immunodeficiency virus (HIV) infection. In this article, they consider the complications of a Th1-Th2 model raised by the nomenclature, discuss the issue of cytokine production by non-T cells, and compare data obtained from T-cell clones with heterogeneous populations of leukocytes from patients. They define Th-cell responses and cytokine profiles as 'type 1' and 'type 2', and reemphasize the importance of strong cellular immune responses, along with the cytokines that augment and maintain such responses, in protective immunity against HIV infection and AIDS progression. Finally, they present a model of activation-induced, cytokine-modulated, programmed cell death as a major factor in the pathogenesis of HIV infection and AIDS.
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