A model for nurse macrophage capabilities and role in HIV-1 pathogenesis.

<p><i>In vitro,</i> we observed that human blood monocytes differentiate into macrophages, and that a portion of these can further develop into what we term “nurse macrophages.” These nurse cells can generate within themselves, CD4+ T-lymphocytes, as well as a previously unknown small monocytoid cell (SRMC). The SRMC, itself, can develop into a nurse macrophage with the ability to give rise to another SRMC. The NM/SRMC cycle, then, represents a form of self-renewal. When cultures of human macrophages are exposed to HIV-1, the SRMC become productively infected, but virus expression does not kill them. Rather, they can differentiate into macrophages, including nurse macrophages, in the presence of virus expression. Thus, a NM/SRMC cycle is established that is characterized by ongoing HIV-1 expression. In the absence of HIV-1 infection, nurse macrophages release resting CD4+ T-cells. The development and release of these lymphocytes is enhanced by treatment with IL-2. When productively infected with HIV-1, the nurse macrophage retains, rather than releases the T-lymphocytes and as a consequence, it takes on the appearance of a multinucleated giant cell. We propose that these events may recapitulate events that occur <i>in vivo</i> and if so, this model offers explanations for HIV-1 persistence and latency.