SUMMARYThe goal of this study was to examine the changes in lymphocyte populations in rectal mucosa during HIV infection and to study their relationship to mucosal immunity and to systemic depletion of CD4 lymphocytes. Rectal biopsies from 58 HIV-infected subjects and eight controls were studied. Frozen rectal tissue sections were stained with antibodies to CD4, CD3, CD8, and markers for macrophages. HIV-infected subjects were divided into early stage (no opportunistic infections) and AIDS groups. There was profound depletion of rectal lamina propria CD4 lymphocytes (16% and 6% of normal content in early and AIDS groups, respectively). However, lymphoid aggregate CD4 lymphocytes were far less severely depleted (69% and 40% of normal content, respectively). The extent of lymphoid aggregate CD4 lymphocyte depletion generally parallelled the CD4 lymphocyte depletion in the blood. CD8 lymphocyte content in both the lamina propria and lymphoid aggregates usually were increased, particularly in early-stage patients. Macrophage contents were usually normal in the HIV-infected groups. We conclude that rectal lamina propria and lymphoid aggregates are distinct compartments differing markedly in their CD4 lymphocyte content during HIV infection. In light of this and an increased number of apoptotic cells which were noted in rectal lamina propria in HIV-infected subjects, we hypothesize that intestinal lamina propria could be a site of rapid CD4 lymphocyte destruction during HIV infection.

DNA topoisomerase II (topo II) is the target of several clinically useful anticancer drugs. Several of these agents, such as doxorubicin and etoposide (VP-16), are used to treat non-Hodgkin's lymphomas (NHL). To understand the therapeutic selectivity of these drugs, a series of 33 cases of NHL for topo II were analyzed using an immunohistochemical technique that detects the enzyme in formalin-fixed, paraffin-embedded tissue. The average topo II index of high grade (Working Formulation) NHL was 48.6 with a range from 24.4 to 79.7. The average topo II index of low grade (Working Formulation) NHL was 4.4 with a range from 0.9 to 11.2. These two values are statistically different (P < .01). The intermediate grade (Working Formulation) NHL are a heterogeneous group based on topo II staining. The average topo II index value for the intermediate grade neoplasms was 26.7 with a range from 1.4 to 54.9. Because the proliferation marker Ki-67 has been shown to be of prognostic importance when used in the analysis of NHL, 27 cases for also were analyzed for MIB1 (Ki-67). The average MIB1 index of the high grade NHL was 59.8 with a range from 40.7 to 80.3. This average is statistically different (P < .01) than the average MIB1 index of 11.2 (range 1.7-28.3) found in the low grade NHL. Similar to results with topo II, the intermediate grade NHL was a heterogeneous group of tumors with respect to MIBI staining and had an average MIB1 index of 49.1 with a range from 8.9 to 86.7. These results show that high grade NHL have topo II and MIB1 indices that are significantly higher than low grade NHL. Intermediate NHL are more heterogeneous and have topo II and MIB1 indices that range from low to high.

Peripheral blood and mucosal compartments are equally responsive to effective antiretroviral therapies. The detection of significant changes within 7 days of starting antiviral therapy implies that intestinal dysfunction may be a direct result of local HIV infection.