Improvement of lymphocyte proliferation in human immunodeficiency virus infection after recombinant interleukin-2 treatment.
In this study, the effect of recombinant interleukin-2 (rIL-2) on the function of peripheral blood mononuclear cells (PBMC) from human immunodeficiency virus (HIV)-infected patients was examined. Using polymerase chain reaction (PCR), an impaired ability of PBMC from 8 patients to respond upon mitogen stimulation with expression of IL-2 and IL-2 receptor (IL-2R) messenger ribonucleic acid (mRNA) was found compared with healthy donors (p = 0.02 and p = 0.05, respectively). Flow cytometry was used to determine the expression of p55 interleukin-2 alpha-receptor (CD25) after phytohaemagglutinin (PHA)-stimulation. Induced CD25 expression in response to stimulation was lower in patient cells than in donor cells (in CD4+ (p = 0.01) and in CD8+ (p = 0.03)). After rlL-2 treatment, the functionality of ex vivo expanded PBMC from patients was restored to the level found in donors. Finally, the induced gene expressions for IL-2 and IL-2R were positively correlated (p < 0.0001), suggesting that the activation of the IL-2 and IL-2R genes in humans may share a common activation pathway, as has been found in monkeys infected by simian immunodeficiency virus (SIV). These results indicate the existence of a reversible IL-2 and IL-2R defect at the pretranscriptional or transcriptional level in PBMC from patients. This may help explain the T-cell anergy found during HIV-infection.
Afzelius
P
P
Department of Infectious Diseases, University of Copenhagen, Hvidovre Hospital, Denmark.
Nielsen
S D
SD
Nielsen
J O
JO
Hansen
J E
JE
D000328:Adult; D018791:CD4 Lymphocyte Count; D018076:DNA, Complementary / Q000096:biosynthesis; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology* / Q000628:therapy*; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics / Q000627:therapeutic use*; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D008214:Lymphocytes / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D010835:Phytohemagglutinins / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000187:drug effects / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000187:drug effects*; D011994:Recombinant Proteins
D018076:DNA, Complementary; D007376:Interleukin-2; D010835:Phytohemagglutinins; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins