Restauración de la inmunidad innata en pacientes con infección por VIH/SIDA después de inicio de terapia antirretroviral / Innate immunity restoration in patients with HIV/AIDS infection associated with antiretroviral therapy

Background: Highly active antiretroviral therapy (HAART) in HIV/AIDS infection induces an important reduction of the viral load (VL) and an immune system reconstitution. CD4+ T lymphocyte count is the immunological measurement commonly used for the follow up of HIV/AIDS patients. Aim: To study prospectively the restoration of the innate immune system in patients with HIV/AIDS infection during their first year on HAART. Patients and Methods: 25 naive HIV/AIDS patients, from San José Hospital and University of Chile Clinical Hospital, Santiago, Chile, were studied between years 2002-2003. Every 4 months after HAART initiation, CD3+, CD4+, CD8+ T lymphocytes and CD16/56+ natural killer (NK) cells were quantified by flow cytometry. NK cell cytotoxicity was measured using radioactive chrome liberation (Cr51). Tumor necrosis factor alpha (TNF-a) and interleukin-10 (IL-10) were measured in peripheral blood mononuclear cells and viral load was determined using Amplicor HIV-1 from Roche Diagnostics Systems. Results: Thirteen of the 25 patients continued in the study. They were all males, average age 35 years old (23-50). At baseline average CD4+ count was 146 cells/µL (31-362) and average viral load was 82.000 copies/mL (4.000-290.000). A raise in CD3+, CD4+, CD8+, and CD16/56 cells was noted at months 9-12 of therapy. Viral load became undetectable in the same period. NK cell function was decreased at the beginning of the therapy (1-4 months), reaching its highest values at months 9-12. There was no significant change in IL-10. TNF-a increased in six patients during the study. Conclusions: In this group of patients, innate immunity was restored during HAART. These results should be confirmed in studies with a longer follow up period and also measuring cytokines such as MIP-1a, MIP-1ß and RANTES.

Actividad citolítica NK en cancer renal y prostático / NK cytolitic activity in renal and prostatic cancer

Natural killer cytolitic activity, the basis of cancer immunotherapy that uses cytolytic cells, may be impaired in cancer. The aim of this work was to study in vitro the natural killer cytolitic activity and its response to the immunomodulators interleukin-2 interferon and phytohemagglutinin stimulated lymphocyte proliferation in a group of 9 patients with renal cell cancer and 6 with prostatic cancer. The results were compared with those of 20 normal volunteers. Twelve patients were operated and were studied twice 48 h and 14 days after surgery. Natural killer cytolitic activity was significantly lower in renal cell and prostatic cancer patients than controls (3.3 ñ 1.6, 4.9 ñ 2.2 and 20.6 ñ 3.7 per cent of specific lysis respectively). This activity was not modified in cancer patients by interleukin-2 50 Ul/ml or interferon 3000 Ul/ml and did not differ in the two postoperative pèriods. Phytohemagglutinin stimulated lymphocyte proliferation was also lower in cancer patients, compared to controls (stimulation index of 18 ñ 3 and 26.5 ñ 5 respectively). It is concluded that these patients have a low immunological level and this study is the first step towards an immunological characterization of cancer patients that are candidate to adoptive immunotherapy

Defectos inmunológicos en el shock séptico: deficiencia de células natural killer y de linfocitos T / Immunological defects in septic shock: deficiency of natural killer cells and T-lymphocytes

It is well fnown that an immunosuppresive rsponse occuts after acute trauma. Some cellular mediators participate in the pathogenesis of septic shock. However, the exact role of the lymphocyte subsets and natural killer (NK) activity in this condition is not clear. We studied NK cytolytic activity through a 51Cr liberation assay using K-562 target cells in 20 patients with initial septic shock (10 men and 10 females, mean age 41 years old). Lymphocyte subsets CD3 (T3), CD4 (T4), CD8 (T8), CD16 (Leu-11) and CD56 (Leu-19) wetre also studied by indirect immunofluorescence. Compared to tesults obtained in 20 healthy volunteers, patient's NK activity was decreased (4.6 ñ 3.9 vs 26.1 ñ 10, p < 0.025), CD16 was lower (10%/187 vs 15%/280 per ul) and CD56 was also lower (6%/120 vs 12%/224 per ul), p < 0,05. T lymphocyte subsers were also decreased: CD3 cells (1100 vs 1352 per ul) and CD4 cells (634 vs 873 per ul), p < 0.05. Thus, a severe decrease in NK cells and NK cell function as well as decreases in CD3 and CD4 lymphocyte subsets are present in the initial stages of septic shock. The predictive value of these findings is currently under study