The hallmark of the effect of HIV infection on host immune response is a progressive reduction in the number of circulating CD4+ lymphocytes or “T-helper” cells. The CD4+ lymphocyte plays a central role in orchestrating both cellular and humoral immune responses. Consequently, as HIV disease becomes progressively more severe, the ability of the host to ward off or contain infecting organisms becomes more and more limited. Many of the immune defects that have been described in HIV-infected persons can be attributed simply to a reduction in numbers of CD4+ lymphocytes. However, HIV infection also induces functional defects in these cells: Circulating CD4+ lymphocytes fail to proliferate in response to antigens that have been encountered previously. This loss of memory may account for failure to continue to contain infections, such as with Mycobacterium tuberculosis or P. carinii, and for the inability to prevent reinfection, as may occur with M. tuberculosis. Reductions in production of interleukin-2 (IL-2) and interferon-gamma by CD4+ lymphocytes from HIV-infected persons have also been demonstrated. These cytokines are responsible for stimulating clonal proliferation of specifically activated alveolar macrophages and lymphocytes. Defects in production of IL-2 and interferon-gamma are detectable early in the course of HIV infection and account for a functional decrease in immune response out of proportion to reduced numbers of circulating CD4+ lymphocytes.

Alveolar macrophages from persons with HIV infection have reduced chemotactic ability, but the ability to phagocytose and kill ingested organisms is thought to be normal. Alveolar macrophages express CD4 surface antigens and thus can be infected with HIV, yet they remain viable. It has been postulated that these cells can serve as reservoirs in which HIV may be sequestered. The protected virions may then infect other cells. It has also been demonstrated that cytokines, especially tumor necrosis factor-alpha and IL-3, stimulated by opportunistic infections such as tuberculosis, result in upregulation of HIV production within macrophages. Given these findings, the alveolar macrophage may play roles in protecting both the host and the virus and may contribute to accelerated HIV disease in the presence of opportunistic infections.