HIV infection and natural killer cytotoxicity in hemophilic patients.
In this study we analyzed the ability of peripheral blood mononuclear cells (PBMC) from hemophilic patients (He) with negative or positive serology for the human immunodeficiency virus (HIV), to increase natural killer (NK) cytotoxicity upon stimulation with physiological and non physiological agents. Purified interleukin-2 (IL-2), the interferon (IFN)-inducer polyinosinic polycytidylic acid (PIC), recombinant alpha- and gamma-IFN and the protein kinase activator phorbol myristate acetate (PMA) were used as stimulatory agents. The NK functional response was correlated with the presence of PBMC bearing phenotypic markers of activated cells (IL-2 receptor, IL-2R) and of different NK cell maturation stages. Our results demonstrate that NK effector cells with slight lytic activity (Leu 7+ CD16-) predominated in HIV+ He patients. On the other hand the occurrence of IL-2R positive cells was similarly high in both HIV+ and HIV- individuals and was probably more related to chronic replacement treatment with Factor VIII or Factor IX concentrates than to HIV infection. The ability to respond to physiological NK regulators such as IL-2 and IFNs, or to the IFN-inducer PIC was impaired in HIV+ He, especially in HIV+ LAS individuals, suggesting that the inability of these cells to increase NK cell activity after appropriate induction was due to an intrinsic defect. Since phosphoinositide turnover and subsequent protein kinase C activation are thought to be part of the physiological mechanism of NK cytotoxicity, we studied the effect of PMA on PBMC from each group of patients. The ability to respond to PMA was lost only in PBMC from HIV+ LAS patients, indicating that impairment of the NK lytic mechanism progresses as the disease gets worse.(ABSTRACT TRUNCATED AT 250 WORDS)
de la Barrera
S S
SS
Instituto de Investigaciones Hematológicas, Academia Nacional de Medicina, Buenos Aires, Argentina.
Olabuenaga
S E
SE
Soria
A
A
Felippo
M
M
Perez Bianco
R
R
de Bracco
M M
MM
D000943:Antigens, Differentiation / Q000032:analysis; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D015658:HIV Infections / Q000150:complications / Q000276:immunology*; D006467:Hemophilia A / Q000150:complications / Q000276:immunology*; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D010641:Phenotype; D015375:Receptors, Interleukin-2 / Q000032:analysis; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000943:Antigens, Differentiation; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D013755:Tetradecanoylphorbol Acetate