title: IL-21 Is Important for Induction of KLRG1+ Effector CD8 T Cells during Acute Intracellular Infection.
abstract: Microsporidia, a latent opportunistic infection associated with mild inflammation, is characterized by a strong CD8 T cell response, which has been shown to be CD4 T cell dependent. In this manuscript, we demonstrate that CD4 help is provided via IL-21 production, a common γ-chain cytokine closely related to IL-2. The peak of IL-21 expression, observed during the acute infection, is associated with an elevated IL-21(+) CD4 T subset, and these cells bear a phenotypic resemblance to T follicular helper cells. We observed that, during per-oral microsporidial infection, IL-21 was critical for the generation of an optimal effector CD8 T cell immunity. Sharply decreased effector KLRG1(+) CD8 response was observed in IL-21R knockout mice, and although these cells exhibited reduced functional properties, they retained the ability to proliferate. The role of IL-21 in the generation of CD8 effectors was cell intrinsic, as stronger defects were observed in the IL-21-deficient compartment from the bone marrow chimeric mice (IL-21R knockout/wild-type). These findings are different from those reported for viral infections in which IL-21 has been primarily associated with the generation and maintenance of CD8 memory response. To the best of our knowledge, this report demonstrates a critical role for IL-21 in the generation of a primary effector CD8 T cell response to an infectious disease model.
authors.affiliation: Department of Microbiology, Immunology and Tropical Medicine, George Washington University, Washington, D.C. 20037.
authors.forename: Magali M
authors.initials: MM
authors.lastname: Moretto
authors.affiliation: Department of Microbiology, Immunology and Tropical Medicine, George Washington University, Washington, D.C. 20037 imti56@gwu.edu.
authors.forename: Imtiaz A
authors.identifier: http://orcid.org/0000-0002-0663-9556
authors.initials: IA
authors.lastname: Khan
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D009670:Encephalitozoon cuniculi / Q000276:immunology*; D016890:Encephalitozoonosis / Q000276:immunology* / Q000469:parasitology; D007378:Interleukins / Q000276:immunology*; D037181:Lectins, C-Type; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011971:Receptors, Immunologic / Q000378:metabolism; D053655:Receptors, Interleukin-21 / Q000235:genetics; D015398:Signal Transduction / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D000098546:Interleukin-21
chemical_list: D007378:Interleukins; C451496:Klrg1 protein, mouse; D037181:Lectins, C-Type; D011971:Receptors, Immunologic; D053655:Receptors, Interleukin-21; D000098546:Interleukin-21