IL-4Ralpha signaling is important for CD8+ T cell cytotoxicity in the absence of CD4+ T cell help.
Cytotoxic CD8(+) T cells are key mediators of viral clearance during primary infection through their production of IFN-gamma and lysis of virally infected cells. Comparatively, the cytokines IL-4 and IL-13 are typically associated with the development of Th2 immune responses against allergens and parasites, while their influence on cytotoxic CD8(+) T cell responses is controversial. We have investigated the roles of IL-4 and IL-13 in the development of CD8(+) T cell responses against influenza infection. We show that in the absence of either IL-4 or IL-13, CD8(+) T cells proliferated and a normal secondary cytotoxic response developed in vitro. In striking contrast, the absence of IL-4Ralpha resulted in impaired ex vivo proliferation and consequently no secondary CTL activity, whereas the in vivo response appeared normal. We show that the presence of CD4(+) T cell help, or the addition of exogenous IL-2 in vitro, restored the response. Taken together, this work reveals previously unrecognized in vivo redundancies between IL-4, IL-13 and IL-2 during immune responses against influenza virus.
Marsland
Benjamin J
BJ
Molecular Biomedicine, Swiss Federal Institute of Technology, Zurich-Schlieren, Switzerland.
Schmitz
Nicole
N
Kopf
Manfred
M
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003601:Cytotoxicity Tests, Immunologic; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D018793:Interleukin-13 / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000276:immunology; D011956:Receptors, Cell Surface; D015534:Trans-Activators / Q000172:deficiency / Q000276:immunology*; D053662:Interleukin-4 Receptor alpha Subunit
D004268:DNA-Binding Proteins; D018793:Interleukin-13; D007376:Interleukin-2; D015847:Interleukin-4; D011956:Receptors, Cell Surface; D015534:Trans-Activators; C504002:Il4ra protein, mouse; D053662:Interleukin-4 Receptor alpha Subunit