Different rates of CD4+ and CD8+ T-cell proliferation in interleukin-2-treated human immunodeficiency virus-positive subjects.
BACKGROUND
Interleukin-2 (IL-2) has been used successfully to increase CD4 cell counts in patients who are human immunodeficiency virus (HIV) positive. The mechanisms involved in this phenomenon are unknown. We hypothesized that a differential proliferation rate of CD4+ compared with CD8+ lymphocytes could be related to the increase of CD4 counts and of CD4/CD8 ratios that occur in HIV+ patients during IL-2 treatment.


METHODS
We enrolled in our study 14 HIV+ patients treated with IL-2 or with highly active antiretroviral therapy (HAART) during a 96-week observation period. Using flow cytometry, we measured longitudinally the expression of the Ki67 antigen in peripheral blood CD4+ and CD8+ lymphocyte subsets.


RESULTS
Compared with HAART alone, IL-2 produced a rapid increase of Ki67+ proliferating CD4 cells and a concomitant increase of the CD4/CD8 ratios, whereas the corresponding CD8 proliferation increased slightly. On the contrary, HAART alone was effective in suppressing equally both CD4 and CD8 proliferation.


CONCLUSIONS
Our results suggest a selective activity of IL-2 on CD4 T-cell proliferation; on the contrary, CD8-specific proliferation is affected minimally during treatment. This information may offer the potential to plan correctly immune activating regimens.
Caggiari
L
L
Division of Microbiology, Immunology and Virology, Centro di Riferimento Oncologico, IRCCS, 33081 Aviano, Italy.
Zanussi
S
S
Crepaldi
C
C
Bortolin
M T
MT
Caffau
C
C
D'Andrea
M
M
De Paoli
P
P
D023241:Antiretroviral Therapy, Highly Active; D017209:Apoptosis / Q000187:drug effects; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D004359:Drug Therapy, Combination; D005434:Flow Cytometry; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D007167:Immunotherapy; D007376:Interleukin-2 / Q000627:therapeutic use*; D019394:Ki-67 Antigen / Q000378:metabolism
D007376:Interleukin-2; D019394:Ki-67 Antigen