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T lymphocytes from 21 untreated patients with acute brucellosis were tested for their proliferative response to polyclonal mitogens. The purified T lymphocytes from these patients showed a defective proliferative response to plant lectins and anti CD3 monoclonal antibodies with respect to the response observed in T lymphocytes from 21 healthy controls (p < 0.05). This defective proliferative response was not corrected by the exogenous addition of interleukin-2 or tumor necrosis factors alpha or beta to the culture medium. After antibiotic therapy, the proliferative response to the mitogens in T lymphocytes was found to be similar to that of the healthy controls (p > 0.05), and significantly higher than that found before treatment (p < 0.05). It was concluded that T lymphocytes from acute brucellosis patients have a defective proliferative response to membrane mitogenic signals, which disappears when the patients are cured after antibiotic treatment.

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The authors investigated the production of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) by phytohaemagglutinin (PHA)-stimulated T-lymphocytes from 21 untreated patients with acute brucellosis. PHA-stimulated T-lymphocytes from acute brucellosis patients showed normal IL-2 production but defective IFN-gamma production (brucellosis patients 531 +/- 103 pg mL-1 vs. healthy controls 1024 +/- 212 pg mL-1) after 72 h of culture. This altered pattern of IL-2 and IFN-gamma production by T-lymphocytes was observed in seven brucellosis patients whose T-lymphocytes exhibited a normal proliferative response to PHA (61 612 +/- 18 422 cpm) as well as in the 14 patients with a defective T-lymphocyte proliferative response to the PHA after 5 days of culture (19 479 +/- 4409 cpm). After antibiotic therapy, production of the two lymphokines by the PHA-stimulated T-lymphocytes from acute brucellosis patients was similar to that of T-lymphocytes from healthy control subjects. The authors conclude that PHA-stimulated T-lymphocytes from untreated patients with acute brucellosis have defective INF-gamma production but normal IL-2 production.

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BACKGROUND: Transitional cell carcinoma (TCC) of the bladder is associated with alterations in the immune system of the host. The authors demonstrated that in patients with bladder carcinoma there is a negative correlation between the levels of natural killer (NK) activity and the clinical evolution and pathologic stages of disease. METHODS: The authors investigated the effect of various doses of recombinant interferon-alpha-2b (IFN-alpha-2b) for variable periods of culture on the nonmajor histocompatibility-restricted cytotoxic activity of peripheral blood mononuclear cells (PBMNC) with or without CD16 and CD3-depleted populations from patients with superficial (confined to the mucosa or lamina propria) and infiltrative (those infiltrating beyond the lamina propria) TCC of the bladder using 4-hour 51-sodium chromate (51Cr)-release cytotoxicity assays against both NK-sensitive (K562) and NK-resistant (JY) tumor target cells. RESULTS: The normal NK activity detected in PBMNC from patients with superficial TCC of the bladder can be significantly enhanced by short-term (18-hour) incubation with recombinant IFN-alpha (P < 0.05). The depressed NK cytotoxic activity found in PBMNC from patients with infiltrative TCC can also be significantly enhanced, but not normalized, by short-term (18-hour) incubation with recombinant IFN-alpha (P < 0.05). Short-term recombinant IFN-alpha-incubated PBMNC from patients with superficial, but not infiltrative, TCC of the bladder also showed marked cytotoxic activity against NK-resistant target cells. By selection with CD16 or CD3 monoclonal antibodies and complement, it was also found that the precursor and effector lymphocytes of this recombinant IFN-alpha-promoted cytotoxicity belong to NK lineage. In kinetic studies, it was found that the maximal levels of the recombinant IFN-alpha-promoted cytotoxic activity against NK-sensitive and NK-resistant target cells in PBMNC from patients with TCC were reached after 18 hours of culture. CONCLUSION: Recombinant IFN-alpha can enhance the nonmajor histocompatibility-restricted cytotoxic activity of PBMNC from patients with TCC of the bladder.

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Researchers have claimed that natural killer (NK) cells are involved in the mechanisms of defense of the host against infections. We have investigated the activity of NK cells in peripheral blood mononuclear cells (PBMNC) from 12 patients for whom acute brucellar infection has been diagnosed and from 14 healthy controls. The sera of eight of the patients were also analyzed 3 months after initiation of a 45-day course of antibiotic treatment, at which time they had no evidence of relapse. PBMNC from patients with acute brucellar infection showed a significantly depressed NK cell activity (P < .01) when compared with those from healthy controls; this depressed activity was not related to a deficient number of NK cells since the numbers of CD56+ and CD16+ cells present in PBMNC were similar in patients and controls. Incubation of PBMNC from patients with acute brucellar infection with recombinant interleukin-2, but not with interferon-gamma, can correct this impaired cytotoxic activity. In treated patients, there was a significant enhancement (P < .05) and normalization of the previously defective NK cell activity. It is concluded that acute brucellar infection is associated with a deficient cytotoxic activity of NK cells that can be overcome by in vitro incubation with interleukin-2 and that reverts to normal after antibiotic treatment.

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Several modifications in the homeostasis of the maternal immune system have been implicated in the survival of the fetoplacental graft. We have investigated the adaptive response of the cytotoxic nonmajor histocompatibility complex (MHC)-restricted effector lymphocytes in pregnancy, and have found that the spontaneous lytic activity against both natural killer (NK)-sensitive and NK-resistant target cells is either decreased or lacking in peripheral blood mononuclear cells (PBMNC) from pregnant women. Recombinant interleukin-2 (rIL-2) normalizes the cytotoxic activity of PBMNC from pregnant women against NK-sensitive target cells in a dose- and time-dependent manner, without modification in the normal amounts of HNK-1+, CD16+ (Leu 11, or CD11b+ (OKM-1) present in these effector populations. However, the pattern of lytic activity against NK-resistant target cells found in PBMNC from pregnant women after short- and long-term incubation with rIL-2 was reduced in comparison with that observed in PBMNC from nongravid women in similar conditions. Moreover, rIL-2 incubation of PBMNC from pregnant subjects was not associated with an enhancement of the lytic binding against NK-resistant target cells. These findings demonstrate that pregnancy is not only associated with a reduction in the NK lytic activity of PBMNC, but also with a reduction in the generation of lymphokine-activated killer activity, in terms of the pattern of lytic activity developed.

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Normal development of pregnancy requires maternal immune system tolerance towards the fetoplacental allograft. Natural Killer (NK) cells can display spontaneous lytic activity against tumoral, and poorly differentiated cells, without a prior sensitization. Moreover this cytotoxic activity is not restricted by the Major Histocompatibility Complex (MHC). We investigated the existence of modifications in the NK activity mediated by peripheral blood mononuclear cells (PBMC) from pregnant women. A significant depression was found in this activity from the first trimester to the puerperium that cannot be ascribed to a defective number of NK cells among pregnant's PBMC. However this impaired NK activity can be reconstituted in vitro by incubation of PBMC with interleukin 2 (IL 2). Pregnancy is also associated with an absence of effectors and/or precursors which mediate other cytotoxic non MHC-restricted activities after long term incubation with IL 2, the so called Lymphokine Activated Killer (LAK) cells.

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