Lymphocytes proliferate in blood and lymph nodes following interleukin-2 therapy in addition to highly active antiretroviral therapy.
BACKGROUND
Substantial redistribution of lymphocytes occurs upon the initiation of highly active antiretroviral therapy (HAART) and immune-based HIV therapies.


OBJECTIVE
To evaluate the relative contribution of apoptosis and proliferation to changes in lymphocyte populations in peripheral blood and lymph node resulting from interleukin-2 (IL-2) therapy in patients receiving stable HAART.


METHODS
Lymphocyte apoptosis was analyzed on various subtypes using fluorescence activated cell sorting with an annexin-V antibody in peripheral blood and by the TUNEL (terminal uridine nucleotide end labelling) method in corresponding lymph node sections. Lymphocyte proliferation was evaluated using an antibody against the cell cycle-associated marker Ki-67 (MIB-1) in peripheral blood and lymph nodes.


RESULTS
A transient increase in apoptosis was seen in peripheral blood and lymph nodes during a cycle of subcutaneous IL-2. A pronounced proliferative effect of IL-2 (from 6.4% of total lymphocytes in patients only treated with HAART to 23.4% in those treated with HAART + IL-2) was detected in peripheral blood, affecting the CD4, CD8 and CD16/56 subsets to a similar extent. Remarkably, the proliferative effect also occurred in lymphoid tissues. While the lymph node structure gradually disintegrated over 24 months in some individuals, the amount of proliferating lymphocytes, including CD4 cells, B cells and follicular dendritic cells, greatly increased upon IL-2, while HIV RNA load in lymph nodes remained unaffected.


CONCLUSIONS
These results show that IL-2 leads to lymphocyte proliferation in peripheral blood and lymph nodes without an impact on viral load in lymphoid tissue. These results have important implications for attempts to reconstitute the immune system in HIV disease.
Hengge
Ulrich R
UR
Department of Dermatology, Venerology and Allergology, University of Essen, Essen, Germany. ulrich.henge@uni-essen.de
Borchard
Carsten
C
Esser
Stefan
S
Schröder
Margit
M
Mirmohammadsadegh
Alireza
A
Goos
Manfred
M
D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D017209:Apoptosis / Q000187:drug effects; D001402:B-Lymphocytes / Q000166:cytology*; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D002455:Cell Division / Q000187:drug effects; D016049:Didanosine / Q000627:therapeutic use; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D015497:HIV-1; D006801:Humans; D007167:Immunotherapy; D007376:Interleukin-2 / Q000627:therapeutic use*; D008198:Lymph Nodes / Q000166:cytology / Q000821:virology; D008297:Male; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D019258:Saquinavir / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000166:cytology*; D015215:Zidovudine / Q000627:therapeutic use
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D007376:Interleukin-2; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine; D016049:Didanosine; D019258:Saquinavir