[Human immunodeficiency virus (HIV) co-receptors expression in mononuclear leucocytes (ML) of HIV+ patients]. / Expresion de co-receptores para el virus de la inmunodeficiencia humana (VIH) luego del cultivo de leucocitos mononucleares (LM) de pacientes VIH+.

Variations of the expression of CXCR4 and CCR5 HIV co-receptors after non stimulated culture of peripheral blood mononuclear cells (PBMC) from HIV+ patients were studied. Expression of CCR5 on both CD4+ and CD8+ T lymphocytes was reduced after 7 days and remained low throughout the culture. CXCR4 levels remained stable in both lymphocyte subpopulations. No significant changes were observed in control HIV- PBMC cultures. In order to ascertain if the CCR5 changes were associated to in vitro HIV replication, 6 days pre-cultured HIV- PBMC were infected with HIV+ culture supernatants. After 3 days CCR5 expression was reduced both in CD4+ and in CD8+ T lymphocytes, while CXCR4 expression was not, coincident with initiation of HIV replication in culture. These results suggest that CCR5 down modulation in CD4+ or CD8+ T lymphocytes is a consequence of HIV replication.

Expresion de co-receptores para el virus de la inmunodeficiencia humana (VIH) luego del cultivo de leucocitos mononucleares (LM) de pacientes VIH+. / [Human immunodeficiency virus (HIV) co-receptors expression in mononuclear leucocytes (ML) of HIV+ patients]

Variations of the expression of CXCR4 and CCR5 HIV co-receptors after non stimulated culture of peripheral blood mononuclear cells (PBMC) from HIV+ patients were studied. Expression of CCR5 on both CD4+ and CD8+ T lymphocytes was reduced after 7 days and remained low throughout the culture. CXCR4 levels remained stable in both lymphocyte subpopulations. No significant changes were observed in control HIV- PBMC cultures. In order to ascertain if the CCR5 changes were associated to in vitro HIV replication, 6 days pre-cultured HIV- PBMC were infected with HIV+ culture supernatants. After 3 days CCR5 expression was reduced both in CD4+ and in CD8+ T lymphocytes, while CXCR4 expression was not, coincident with initiation of HIV replication in culture. These results suggest that CCR5 down modulation in CD4+ or CD8+ T lymphocytes is a consequence of HIV replication.

[Apoptosis and human immunodeficiency virus infection (HIV]. / Apoptosis e infección por el virus de la inmunodeficiencia humana (HIV).

Generalized activation of the immune system after HIV infection leads to an exacerbation of all apoptotic mechanisms. CD4+, CD8+ T lymphocytes and B lymphocytes are sensitized to apoptotic stimuli. Macrophages are important in the removal of apoptotic cells, they prevent apoptotic cell accumulation during in vitro culture and they may lead to enhanced CD4+ T lymphocyte cell death through indirect mechanisms. A simple procedure for prolonged culture of peripheral blood mononuclear cells from HIV+ patients is discussed, in relation to its convenience to evaluate apoptosis, cell to cell interaction and HIV replication in the absence of exogenously added stimuli or co-culture of allogeneic cells. In this system, HIV replication takes place primarily in cells of macrophage lineage that may be activated into differentiation through removal of apoptotic debris during the culture.

Apoptosis e infección por el virus de la inmunodeficiencia humana (HIV) / [Apoptosis and human immunodeficiency virus infection (HIV]

Generalized activation of the immune system after HIV infection leads to an exacerbation of all apoptotic mechanisms. CD4+, CD8+ T lymphocytes and B lymphocytes are sensitized to apoptotic stimuli. Macrophages are important in the removal of apoptotic cells, they prevent apoptotic cell accumulation during in vitro culture and they may lead to enhanced CD4+ T lymphocyte cell death through indirect mechanisms. A simple procedure for prolonged culture of peripheral blood mononuclear cells from HIV+ patients is discussed, in relation to its convenience to evaluate apoptosis, cell to cell interaction and HIV replication in the absence of exogenously added stimuli or co-culture of allogeneic cells. In this system, HIV replication takes place primarily in cells of macrophage lineage that may be activated into differentiation through removal of apoptotic debris during the culture.

Apoptosis e infección por el virus de la inmunodeficiencia humana (HIV). / [Apoptosis and human immunodeficiency virus infection (HIV]

Generalized activation of the immune system after HIV infection leads to an exacerbation of all apoptotic mechanisms. CD4+, CD8+ T lymphocytes and B lymphocytes are sensitized to apoptotic stimuli. Macrophages are important in the removal of apoptotic cells, they prevent apoptotic cell accumulation during in vitro culture and they may lead to enhanced CD4+ T lymphocyte cell death through indirect mechanisms. A simple procedure for prolonged culture of peripheral blood mononuclear cells from HIV+ patients is discussed, in relation to its convenience to evaluate apoptosis, cell to cell interaction and HIV replication in the absence of exogenously added stimuli or co-culture of allogeneic cells. In this system, HIV replication takes place primarily in cells of macrophage lineage that may be activated into differentiation through removal of apoptotic debris during the culture.

[Apoptosis. Its role in the immune system ontogeny and in HIV infection]. / Apoptosis. Su papel en la ontogenia del sistema inmune y en la infección por HIV.

Apoptosis is a physiologic process whereby undesired cells are eliminated in a non-inflammatory way. It is characterized by cellular retraction, clumping of nuclear chromatin and DNA retraction followed by DNA degradation into oligonucleosomes formed by 180-185 base pairs or multiples of these units that can be identified electrophoretically. The plasma membrane and organelles are well conserved until the final stages of the process. Apoptosis is central to many of the functions of the immune system. A review of its role in the immune system as well as in AIDS is presented, as well as a brief description of the methodology that can be followed for the assay of apoptosis.

Apoptosis. Su papel en la ontogenia del sistema inmune y en la infección por HIV. / [Apoptosis. Its role in the immune system ontogeny and in HIV infection]

Apoptosis is a physiologic process whereby undesired cells are eliminated in a non-inflammatory way. It is characterized by cellular retraction, clumping of nuclear chromatin and DNA retraction followed by DNA degradation into oligonucleosomes formed by 180-185 base pairs or multiples of these units that can be identified electrophoretically. The plasma membrane and organelles are well conserved until the final stages of the process. Apoptosis is central to many of the functions of the immune system. A review of its role in the immune system as well as in AIDS is presented, as well as a brief description of the methodology that can be followed for the assay of apoptosis.

T-cell-mediated cytotoxicity against Mycobacterium antigen-pulsed autologous macrophages in leprosy patients.

The involvement of CD4+ T lymphocytes in the defense mechanisms against intracellular pathogens is widely recognized. Little information is available on the generation and specificity of the cytotoxic cells that eliminate human monocytes/macrophages infected with mycobacteria. In this work, we tested whether mononuclear cells from leprosy patients could generate cytotoxic T-cell activity against autologous macrophages pulsed with Mycobacterium leprae or purified protein derivative (PPD) in a 4-h 51Cr release assay. Peripheral blood mononuclear cells from normal Mycobacterium bovis BCG-immunized controls or from leprosy patients stimulated with antigen for 7 days were used as effector cells. Paucibacillary (PB) patients and normal controls yielded more active effector cells in this system than multibacillary (MB) patients. MB patients were able to develop cytotoxicity against M. leprae, BCG, or PPD, in contrast with the immunological anergy widely described. We did not find cytotoxicity against unpulsed macrophages. Cross-reactivity was observed between PPD, BCG, and M. leprae. Only antigen-pulsed autologous macrophages were suitable as target cells. M. leprae-induced cytotoxic cells were found in both CD4+ CD8- and CD4- CD8+ T-cell subsets, whereas CD4+ cells were the main component of PPD-induced cytotoxicity. In MB patients, BCG-induced cytotoxic cells were better killers of M. leprae-pulsed macrophages than cells induced by M. leprae. This is an interesting finding in view of the ongoing vaccination trials. The involvement of CD4- or CD8-mediated cytotoxicity may be important in the balance between protection and tissue or nerve damage.

Effect of lymphokines on natural killer cytotoxicity in patients with high risk of developing the acquired immune deficiency syndrome.

Regulation of natural killer (NK) activity of peripheral blood mononuclear cells (PBMC) from patients with the acquired immune deficiency syndrome (AIDS) and from individuals at high risk of developing AIDS (R-AIDS) was studied. The response of untreated PBMC to the interferon inducer polyinosinic polycytidilic acid (Poly I:C) was lower in AIDS and R-AIDS than in normal controls and PBMC from R-AIDS were more susceptible to stimulation with lymphokine rich supernatants (Con A-SN, PHA-SN, lectin free IL-2) than AIDS and normal controls. To determine the role of the different T lymphocyte subsets in the regulation of NK activity, PBMC were selectively treated with monoclonal non-cytotoxic anti-Leu 2a and anti-Leu 3a antibodies and then stimulated with lymphokine rich supernatants. These results indicate that the effect of crude supernatants was the combination of opposite effects. Leu 2a-blocked R-AIDS-PBMC enhanced NK cytotoxicity when exposed to IL-2 rich supernatants whereas Leu 3a-blocked R-AIDS-PBMC suppressed the cytotoxic reaction.