Effects of interleukin-2 therapy on the proliferation and differentiation of CD4/CD25 positive and CD4/CD25 negative cells in HIV+ patients.
Interleukin-2 has been widely used in HIV-1+ subjects as an immunoactivating agent. In this study, we investigated cytokine production, Ki67 antigen expression and the modulation of the surface phenotype of the CD4/CD25+ subset as compared to the reciprocal CD4/CD25- subset in IL-2-treated HIV+ patients. Our findings suggest that CD4 T cells are heterogeneous in responding to IL-2, because CD4/CD25+ cells sharply increased their "memory" phenotype, their Ki67 antigen expression and were the main in vivo targets for IL-2-dependent proliferation during therapy, while the percentages of IFN-gamma+ (terminally differentiated) cells remained unchanged at the end of therapy. Conversely, the CD4+/CD25- subpopulation showed an expansion of differentiated cells and a slight increase in the proliferation rate. The use of anti-retroviral therapy alone (HAART) reduced the proliferation and increased the differentiation of both CD4 subsets. Our data suggest that IL-2 has a moderate capacity to activate resting T cells in vivo and is probably unable to boost HIV-1 from latency to the replicative state.
Caggiari
L
L
Microbiology, Immunology and Virology, Centro di Riferimento Oncologico, Aviano, Italy.
Zanussi
S
S
D'Andrea
M
M
Bortolin
M T
MT
Crepaldi
C
C
Caffau
C
C
Paoli
P D
PD
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects*; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D019469:Indinavir / Q000008:administration & dosage; D007371:Interferon-gamma / Q000096:biosynthesis / Q000187:drug effects; D007376:Interleukin-2 / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D011994:Recombinant Proteins / Q000008:administration & dosage
D019380:Anti-HIV Agents; D016207:Cytokines; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D019469:Indinavir; D007371:Interferon-gamma; C082598:aldesleukin