title: Antiviral immune responses in Itk-deficient mice.
abstract: Mice lacking Itk, a T-cell-specific protein tyrosine kinase, have reduced numbers of T cells and reduced responses to allogeneic major histocompatibility molecules. This study analyzed antiviral immune responses in mice deficient for Itk. Primary cytotoxic T-lymphocyte (CTL) responses were analyzed after infection with lymphocytic choriomeningitis virus (LCMV), vaccinia virus (VV), and vesicular stomatitis virus (VSV). Ex vivo CTL activity was consistently reduced by a factor of two to six for the different viruses. CTL responses after restimulation in vitro were similarly reduced unless exogenous cytokines were added. In the presence of interleukin-2 or concanavalin A supernatant, Itk-deficient and control mice responded similarly. Interestingly, while LCMV was completely eliminated by day 8 in both Itk-deficient and control mice, VV cleared from itk-/- mice with delayed kinetics. Antibody responses were evaluated after VSV infection. Both the T-cell-independent neutralizing immunoglobulin M (IgM) and the T-cell-dependent IgG responses were similar in Itk-deficient and control mice. Taken together, the results show that CTL responses are reduced in the absence of Itk whereas antiviral B-cell responses are not affected.
authors.affiliation: Department of Pathology, University of Zurich, Switzerland.
authors.forename: M F
authors.initials: MF
authors.lastname: Bachmann
authors.forename: D R
authors.initials: DR
authors.lastname: Littman
authors.forename: X C
authors.initials: XC
authors.lastname: Liao
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D008285:Major Histocompatibility Complex; D051379:Mice; D018345:Mice, Knockout; D011505:Protein-Tyrosine Kinases / Q000172:deficiency* / Q000235:genetics; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D013997:Time Factors; D014616:Vaccinia virus / Q000276:immunology*; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D016207:Cytokines; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011505:Protein-Tyrosine Kinases; C080813:emt protein-tyrosine kinase