The observation that IL-10 alters NK receptor expression similar to that observed in HIV infection, and the fact that NK receptor expression and activity normalize in parallel with ART-induced reduction of circulating IL-10 levels supports a role for IL-10 in NK cell activity and HIV immunopathogenesis.

Antiretroviral treatment of patients infected with HIV results in improvements in CD4+ T cell number. Emerging evidence suggests that some of the improvements in CD4+ T cell number that occur in response to protease inhibitor (PI) therapy may not be accounted for solely by enhanced viral suppression, implying that PI may directly affect T cell survival. Since HIV T cell depletion is associated with enhanced apoptosis, we analyzed the effect of PIs on T cell apoptosis. In vitro treatment of peripheral blood lymphocytes (PBLs) from HIV-infected but untreated patients with reverse transcriptase inhibitors (RTIs) does not alter apoptosis, whereas PI treatment rapidly reduces CD4+ and CD8+ T cell apoptosis. In contrast, PI treatment does not alter apoptosis in PBL blasts from HIV-negative patients, or in Jurkat T cells. Consistent with this observation, 8 days of PI therapy in HIV-infected patients does not significantly alter plasma viremia, yet results in significant inhibition of CD4+ and CD8+ T cell apoptosis. The inhibitory effects of PI on apoptosis have implications concerning the treatment of HIV and its pathogenesis.

Damage to the immune and hematopoietic systems following exposure to ionizing radiation, whether accidental or for therapeutic purposes, renders victims susceptible to opportunistic infections and diseases. Elucidating a reliable biological indicator or “biological dosimeter” to indicate rapidly the extent of injury sustained by an individual would be desirable. Total leukocyte count has been used historically as an indicator of immune damage, but it is not truly indicative of functional immunity post‐irradiation. A flow cytometric (FCM) technique was developed to determine whether a rapid reproducible assay could be developed to assess the extent of radiation damage. To this end, peripheral blood leukocyte populations and subpopulations were monitored. C57BL/6 mice were exposed to 100‐, 400‐, or 700‐cGy whole‐body γ‐irradiation (WBI) and blood samples were collected from the retro‐orbital sinus 1, 4, and 7 days post‐irradiation. The blood samples were prepared for FCM by incubation with monoclonal antibodies (mAb) to various murine leukocyte CD surface markers. The results show that the proportion of CD4+ T lymphocytes increased approximately 2‐fold on day 4 after 700 cGy, the proportion of B lymphocytes declined markedly at all doses relative to unirradiated controls, and natural killer (NK) cells rose dramatically (9‐fold) by day 4 after 700 cGy. The patterns of alteration in the relative proportions of peripheral blood mononuclear cells (PBMC) populations observed post‐irradiation, particularly in B lymphocytes and natural killer (NK) cells, seem to represent potent and consistent indicators of immune damage, allowing some inference as to the immune competence of the individual. Cytometry 31:45–52, 1998. © 1998 Wiley‐Liss, Inc.

No abstract

Damage to the immune and hematopoietic systems following exposure to ionizing radiation, whether accidental or for therapeutic purposes, renders victims susceptible to opportunistic infections and diseases. Elucidating a reliable biological indicator or "biological dosimeter" to indicate rapidly the extent of injury sustained by an individual would be desirable. Total leukocyte count has been used historically as an indicator of immune damage, but it is not truly indicative of functional immunity post-irradiation. A flow cytometric (FCM) technique was developed to determine whether a rapid reproducible assay could be developed to assess the extent of radiation damage. To this end, peripheral blood leukocyte populations and subpopulations were monitored. C57BL/6 mice were exposed to 100-, 400-, or 700-cGy whole-body gamma-irradiation (WBI) and blood samples were collected from the retro-orbital sinus 1, 4, and 7 days post-irradiation. The blood samples were prepared for FCM by incubation with monoclonal antibodies (mAb) to various murine leukocyte CD surface markers. The results show that the proportion of CD4+ T lymphocytes increased approximately 2-fold on day 4 after 700 cGy, the proportion of B lymphocytes declined markedly at all doses relative to unirradiated controls, and natural killer (NK) cells rose dramatically (9-fold) by day 4 after 700 cGy. The patterns of alteration in the relative proportions of peripheral blood mononuclear cells (PBMC) populations observed post-irradiation, particularly in B lymphocytes and natural killer (NK) cells, seem to represent potent and consistent indicators of immune damage, allowing some inference as to the immune competence of the individual.