The overall objective of this research proposal is to learn how MHC class-II restricted T cells (vis. Th) induce and regulate the immune response to influenza virus. We have approached this, during the previous granting period, by generating virus-specific Th clones from BALB/c mice through longterm culture and by sub- sequently testing the function of some of these Th clones in the promotion of anti-viral B cell responses in vivo after their adoptive transfer into athymic BALB/c recipient mice. We now propose to more fully explore this experimental system as follows: First, we plan to make a comprehensive determination of the factor profile (IL-2, IL-3, IL-4, IL-5, IL-6, IFN-gamma, LT, TNF) of all presently available Th clones by Northern blot analyses. Should the Th panel lack members of a defined Th subset, such as Th2, we then would make attempts to generate these additional Th clones. Examples of Th clones with clearly distinct factor profiles, such as Thi, Th2 and perhaps additional ones, will be tested for function in vivo after adoptive transfer into suitable recipient mice. This will include tests for promotion of i) B cell responses. ii) cytotoxic T cell responses. iii) memory B cell formation and iv) virus clearance. Selected Th clones will be studied also for survival in vivo and for migration and homing properties. We hope that this analysis will provide us with new insights into the functions of Th in the induction and regulation of an anti-viral immune response and of anti-viral defense mechanisms in vivo.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
4R37AI013989-18
Application #
2060032
Study Section
Special Emphasis Panel (NSS)
Project Start
1977-04-01
Project End
1998-12-31
Budget Start
1994-04-01
Budget End
1994-12-31
Support Year
18
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Wistar Institute
Department
Type
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Mozdzanowska, Krystyna; Feng, Jingqi; Eid, Mark et al. (2006) Enhancement of neutralizing activity of influenza virus-specific antibodies by serum components. Virology 352:418-26
Zharikova, Darya; Mozdzanowska, Krystyna; Feng, Jingqi et al. (2005) Influenza type A virus escape mutants emerge in vivo in the presence of antibodies to the ectodomain of matrix protein 2. J Virol 79:6644-54
Mozdzanowska, Krystyna; Furchner, Michelle; Zharikova, Darya et al. (2005) Roles of CD4+ T-cell-independent and -dependent antibody responses in the control of influenza virus infection: evidence for noncognate CD4+ T-cell activities that enhance the therapeutic activity of antiviral antibodies. J Virol 79:5943-51
Mozdzanowska, Krystyna; Feng, JinQi; Eid, Mark et al. (2003) Induction of influenza type A virus-specific resistance by immunization of mice with a synthetic multiple antigenic peptide vaccine that contains ectodomains of matrix protein 2. Vaccine 21:2616-26
Feng, Jing Qi; Mozdzanowska, Krystyna; Gerhard, Walter (2002) Complement component C1q enhances the biological activity of influenza virus hemagglutinin-specific antibodies depending on their fine antigen specificity and heavy-chain isotype. J Virol 76:1369-78
Mozdzanowska, K; Maiese, K; Gerhard, W (2000) Th cell-deficient mice control influenza virus infection more effectively than Th- and B cell-deficient mice: evidence for a Th-independent contribution by B cells to virus clearance. J Immunol 164:2635-43
Mozdzanowska, K; Maiese, K; Furchner, M et al. (1999) Treatment of influenza virus-infected SCID mice with nonneutralizing antibodies specific for the transmembrane proteins matrix 2 and neuraminidase reduces the pulmonary virus titer but fails to clear the infection. Virology 254:138-46
Mozdzanowska, K; Furchner, M; Washko, G et al. (1997) A pulmonary influenza virus infection in SCID mice can be cured by treatment with hemagglutinin-specific antibodies that display very low virus-neutralizing activity in vitro. J Virol 71:4347-55
Mozdzanowska, K; Furchner, M; Maiese, K et al. (1997) CD4+ T cells are ineffective in clearing a pulmonary infection with influenza type A virus in the absence of B cells. Virology 239:217-25
Gerhard, W; Mozdzanowska, K; Furchner, M et al. (1997) Role of the B-cell response in recovery of mice from primary influenza virus infection. Immunol Rev 159:95-103

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