Interleukin-2 immunotherapy exerts a differential effect on CD4 and CD8 T cell dynamics.
BACKGROUND
Emerging evidence indicates that CD4 and CD8 T cell recovery is differentially regulated during HIV infection. The hallmark of interleukin-2 (IL-2)-induced immune reconstitution is the selective outgrowth of CD4 through undefined mechanisms.


OBJECTIVE
To delineate the effect of IL-2 on T cell homeostasis by analysing the differential impact of IL-2 immunotherapy on CD4 and CD8 dynamics.


METHODS
A randomized trial of 15 HIV-positive patients, eight receiving IL-2 immunotherapy with highly active antiretroviral therapy (HAART) and seven with HAART alone. Patients were followed for a 48-week period following three IL-2 cycles (overall, 10 weeks in duration).


METHODS
CD4 and CD8 count, naive and memory immunophenotype, proliferation by Ki67, and CD8+CD38+ activated pattern were measured longitudinally by flow cytometry. Thymic output contribution to both CD4 and CD8 was evaluated by measurement of T cell receptor excision circles (TREC). Wilcoxon test was used to compare results.


RESULTS
Compared with changes seen with HAART alone, IL-2 induced a more significant rise in CD4 than CD8 T cell count (P < 0.01), associated with a significant increase in Ki67-proliferating CD4 (P < 0.05), whereas no changes were seen in CD8+Ki67+ (P > 0.05). Furthermore, IL-2 administration was associated with CD4 TREC increase, whereas CD8 TREC remained stable (P > 0.05). Modifications in CD4 and CD8 T cells seen in patients taking only HAART were not associated with changes in CD4 and CD8 TREC.


CONCLUSIONS
By showing a differential impact on CD4 and CD8 homeostasis, the study suggests that IL-2-associated immune reconstitution results from protean interactions between T cell compartments; this has significant implications for the correct planning of immunotherapeutic strategies.
Marchetti
Giulia
G
Institute of Infectious Diseases and Tropical Medicine, Luigi Sacco Hospital, University of Milan, Italy.
Meroni
Luca
L
Molteni
Chiara
C
Bandera
Alessandra
A
Franzetti
Fabio
F
Galli
Massimo
M
Moroni
Mauro
M
Clerici
Mario
M
Gori
Andrea
A
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002455:Cell Division; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D006706:Homeostasis / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007376:Interleukin-2 / Q000276:immunology / Q000627:therapeutic use*; D018655:Lymphocyte Count; D008875:Middle Aged; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism
D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell