An Alternative View of the Th1/Th2 Switch Hypothesis in HIV Infection

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Abstract
A theory that seeks to explain what induces the relentless progression of HIV-infected subjects to AIDS has received considerable attention. This theory holds that HIV infection results in a Th1/Th2 switch. However, analysis of constitutive cytokine mRNA expression in lymphoid tissues from HIV-infected individuals did not confirm an in vivo Th1/Th2 switch. Moreover, data available at the level of in vitro-stimulated peripheral blood mononuclear cells or cloned T cells do not provide clear evidence for a definite switch to the Th2 responses in any HIV-infected subject and in any phase of HIV infection. At most, currently available data on the profile of cytokines released in response to in vitro stimulation suggest a Th1-to-Th0 shift in a proportion of memory CD4+ T cells. On the other hand, experiments of in vitro infection with HIV of already established CD4+ T cell clones indicated that Th2 and Th0 cells support HIV replication better than Th1 cells, suggesting that early destruction of Th2 cells by direct or indirect HIV-mediated cell killing may occur. Finally, in some HIV-infected individuals with low CD4+ T cell counts, a prevalence of CD8+ T cells producing type 2 cytokines was found in both peripheral blood and skin. Thus, although the induction of a general Th2 state in HIV infection is not proven, enhanced production of type 2 cytokines may occur in a proportion of HIV-infected individuals and play some role in the pathogenesis of the disease.