Activation, survival and apoptosis of CD45RO+ and CD45RO- T cells of human immunodeficiency virus-infected individuals: effects of interleukin-15 and comparison with interleukin-2.
HIV infection is associated with increased representation of T cells bearing an activated, memory (CD45RO+) phenotype. Although administration of antiretroviral agents and interleukin-2 (IL-2) augment depleted CD4+ T-cell numbers, such therapies have been preferentially beneficial for CD45RO+ T cells. Interleukin-15 (IL-15) exhibits many biological activities in common with IL-2, including promoting T-cell survival and proliferation. The present study found that these two cytokines differed in their ability to induce proliferation, enhance survival, and control apoptosis of CD45RO+ and CD45RO- T-cell populations of human immunodeficiency- (HIV) infected individuals. When used at equivalent concentrations in vitro, IL-15 was more potent than IL-2 in activating and stimulating proliferation of CD4+CD45RO+, CD8+CD45RO+ and CD8+CD45RO- cells, but failed to be more effective than IL-2 in reducing apoptosis. Poor activation of CD4+CD45RO- cells by IL-15 and to IL-2 appeared to be attributable to low expression of the beta receptor chain utilized by both cytokines. However, IL-15 was more effective than IL-2 in enhancing survival of the CD4+CD45RO- population, suggesting a greater protective effect of IL-15 for naive CD4+ T cells, which are preferentially lost in HIV-infected individuals.
Naora
H
H
Unite d'Oncologie Virale, Departement SIDA et Retrovirus, Institut Pasteur, 28, rue du Docteur Roux, 75724 Paris Cedex 15, France.
Gougeon
M
M
D017209:Apoptosis / Q000276:immunology; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D019409:Interleukin-15 / Q000276:immunology*; D007376:Interleukin-2 / Q000276:immunology*; D017493:Leukocyte Common Antigens / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D019409:Interleukin-15; D007376:Interleukin-2; D017493:Leukocyte Common Antigens