Monoclonal antibody against IFN-gamma inhibits Moloney murine sarcoma virus-specific cytotoxic T lymphocyte differentiation
The role of autochthonous IFN- production was evaluated in immune reactions to Moloney murine sarcoma virus (M-MSV)-induced tumors which are characterized by spontaneous regression mainly caused by virus-specific CTL activity. A functional IFN- depletion, induced by repeated administration of mAb anti-IFN- at the site of virus inoculation, prevented tumor regression in M-MSV-injected mice. Moreover, this antibody inhibited in vitro both proliferation and differentiation of M-MSV-specific T lymphocytes obtained in bulk cultures, but not growth and lytic activity of the already differentiated virus-specific CTL clone CHM-14 stimulated with rIL-2 and relevant tumor Ag. In addition, in mice receiving mAb treatment the frequency of M-MSV-specific CTL precursors, evaluated by means of limiting dilution analysis, was strongly reduced in comparison with that of control mice injected only with virus. Because CTL secrete IFN- following antigenic stimulation, the possibility that non-T effector cells recruited by this lymphokine might mediate tumor regression was also considered. Adoptive immunotherapy experiments, performed in T cell-deficient (Tx + BM) and in sublethally irradiated mice, demonstrated that transfer of CHM-14 CTL clone, which secretes IFN-, was able to counteract M-MSV tumor growth despite the local mAb anti-IFN- treatment which may have prevented host cell recruitment. Moreover, repeated local rIFN- inoculations in Tx + BM mice did not counteract M-MSV tumor progression, thus confirming that other IFN- properties such as non-T cell recruitment, antiviral or anti-proliferative IFN- activities have little or no relevance when M-MSV-specific CTL are lacking. On the whole, these results indicate that in M-MSV-injected mice, tumor enhancement after mAb anti-IFN- treatment is principally caused by impaired differentiation of virus-specific CTL precursors.
- Research Organization:
- Univ. of Padova (Italy)
- OSTI ID:
- 5198184
- Journal Information:
- J. Immunol.; (United States), Vol. 140:4
- Country of Publication:
- United States
- Language:
- English
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INTERFERON
BIOSYNTHESIS
LYMPHOCYTES
CELL DIFFERENTIATION
MONOCLONAL ANTIBODIES
BIOLOGICAL FUNCTIONS
EXPERIMENTAL NEOPLASMS
IMMUNE REACTIONS
MICE
RADIATION CHIMERAS
SARCOMAS
VIRUSES
ANIMAL CELLS
ANIMALS
ANTIBODIES
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CHIMERAS
CONNECTIVE TISSUE CELLS
DISEASES
FUNCTIONS
GROWTH FACTORS
LEUKOCYTES
LYMPHOKINES
MAMMALS
MATERIALS
MICROORGANISMS
MITOGENS
MOSAICISM
NEOPLASMS
ORGANIC COMPOUNDS
PARASITES
PROTEINS
RODENTS
SOMATIC CELLS
SYNTHESIS
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560152* - Radiation Effects on Animals- Animals