Efficient induction of primary and secondary T cell-dependent immune responses in vivo in the absence of functional IL-2 and IL-15 receptors.
IL-2 and IL-15 are thought to be important cytokines for T cell-dependent immune responses. Mice deficient in IL-2, IL-2Ralpha, and IL-2Rbeta are each characterized by a rapid lethal autoimmune lymphoproliferative disorder that complicates their use in studies aimed at investigating the role of these cytokines and receptors for immune responses in vivo. We have previously characterized a novel transgenic (Tg) mouse on the IL-2Rbeta-/- genetic background (Tg-/- mice) that lacks autoimmune disease but still contains peripheral T cells that are nonresponsive to IL-2 and IL-15. In the present study, these mice were used to investigate the extent by which IL-2 and IL-15 are essential for T cell immunity in vivo. Tg-/- mice generated near normal primary and secondary Ab responses to OVA, readily mounted first and second set allogeneic skin graft rejection responses, and developed primary and recall CD8 T cell responses to vaccinia virus. However, Tg-/- mice generated a slightly lower level of IgG2a Abs to OVA, exhibited a somewhat delayed first set skin graft rejection response with lower allo-specific CTL, and developed a significantly lower number of IFN-gamma-producing vaccinia-specific CD8+ T cells. Thus, although T effector function is somewhat impaired, T cell immunity is largely functional in the absence of IL-2- and IL-15-induced signaling through IL-2Rbeta.
Yu
Aixin
A
Department of Microbiology and Immunology, University of Miami School of Medicine, Miami, FL 33101, USA.
Zhou
Jiehao
J
Marten
Norman
N
Bergmann
Cornelia C
CC
Mammolenti
Michele
M
Levy
Robert B
RB
Malek
Thomas R
TR
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000917:Antibody Formation / Q000235:genetics; D017252:CD3 Complex / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D006084:Graft Rejection / Q000235:genetics; D007114:Immunization; D007117:Immunization, Secondary; D007074:Immunoglobulin G / Q000096:biosynthesis; D019409:Interleukin-15 / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D006517:Murine hepatitis virus / Q000276:immunology; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2 / Q000172:deficiency* / Q000235:genetics*; D016038:Skin Transplantation / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014184:Transplantation, Homologous; D014616:Vaccinia virus / Q000276:immunology
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; C508025:Il15ra protein, mouse; D007074:Immunoglobulin G; D019409:Interleukin-15; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2; D010047:Ovalbumin