Interleukin-21 and cellular activation concurrently induce potent cytotoxic function and promote antiviral activity in human CD8 T cells.
Infection with human immunodeficiency virus (HIV)-1 induces a progressive deterioration of the immune system that ultimately leads to acquired immune deficiency syndrome (AIDS). Murine models indicate that the common γ-chain (γ(c))-sharing cytokine interleukin (IL)-21 and its receptor (IL-21R) play a crucial role in maintaining polyfunctional T cell responses during chronic viral infections. Therefore, we analyzed the ability of this cytokine to modulate the properties of human CD8 T cells in comparison with other γ(c)-sharing cytokines (IL-2, IL-7, and IL-15). CD8 T cells from healthy volunteers were stimulated in vitro via T cell receptor signals to mimic the heightened status of immune activation of HIV-infected patients. The administration of IL-21 upregulated cytotoxic effector function and the expression of the costimulatory molecule CD28. Notably, this outcome was not accompanied by increased cellular proliferation or activation. Moreover, IL-21 promoted antiviral activity while not inducing HIV-1 replication in vitro. Thus, IL-21 may be a favorable molecule for immunotherapy and a suitable vaccine adjuvant in HIV-infected individuals.
Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, Florida, USA.
Anita
A
Parmigiani
Maria F
MF
Pallin
Helena
H
Schmidtmayerova
Mathias G
MG
Lichtenheld
Savita
S
Pahwa
D000276:Adjuvants, Immunologic / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D018106:CD28 Antigens / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D053804:Granzymes / Q000032:analysis; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D019409:Interleukin-15 / Q000276:immunology / Q000494:pharmacology; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism; D015851:Interleukin-7 / Q000276:immunology / Q000378:metabolism; D007378:Interleukins / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D054353:Perforin / Q000032:analysis; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects / Q000276:immunology; D000098546:Interleukin-21
D000276:Adjuvants, Immunologic; D018106:CD28 Antigens; D019409:Interleukin-15; D007376:Interleukin-2; D015851:Interleukin-7; D007378:Interleukins; D011948:Receptors, Antigen, T-Cell; D054353:Perforin; D053804:Granzymes; D000098546:Interleukin-21