Natural-killer cell-derived cytolytic molecules in HIV-associated pulmonary tuberculosis-role of exogenous interleukins.
OBJECTIVE
The ability of NK cells to produce cytolytic molecules is impaired during HIV infection. The objective of the present study is to investigate whether impairment in production of innate cytokines in HIV-infected individuals is responsible for the defective NK cytolytic response.


METHODS
The study included 30 subjects each of normal healthy subjects, pulmonary tuberculosis patients, HIV-infected individuals, and patients with HIV and TB co-infection. Intracellular staining method was adopted to enumerate the NK cells positive for cytolytic molecules. Highest stimulation of cytolytic molecules was seen with IL-15 + IL-12 combination.


RESULTS
Stimulation with IL-15 + IL-12 showed an increased expression of perforin in NHS and HIV groups. Granzyme A was stimulated only in HIV, even with IL-15 + IL-12. Among the cytolytic molecules, maximal stimulation with IL-15 + IL-12 was seen for Granyme A and Granzyme B. Both the HIV and HIV-TB groups showed an increased response with IL-15 + IL-12 for granulysin.


CONCLUSIONS
Supplementing IL-15 + IL-12 in vitro increased the number of NK cells that are expressing cytolytic molecules in HIV-infected individuals but in HIV-TB, the critical cytolytic molecule, perforin is not apparent perhaps due to the influence of TB on HIV.
Department of Immunology, Tuberculosis Research Centre (ICMR), Mayor V. R. Ramanathan Road, Chetput, Chennai, 600 031, India.
P V Ramana
PV
Rao
S
S
Ramanavelan
S
S
Rajasekaran
Alamelu
A
Raja
D000328:Adult; D055252:Cell-Derived Microparticles / Q000378:metabolism; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D053804:Granzymes / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D006678:HIV / Q000276:immunology* / Q000472:pathogenicity; D015658:HIV Infections / Q000150:complications / Q000276:immunology*; D006801:Humans; D007378:Interleukins / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D054353:Perforin / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology*; D014397:Tuberculosis, Pulmonary / Q000150:complications / Q000276:immunology*
D007378:Interleukins; D011994:Recombinant Proteins; D054353:Perforin; D053804:Granzymes