Interferon-gamma is not an antiviral, but a growth-promoting factor for T lymphocytes.
The effects of interferon (IFN)-gamma or IFN-alpha/beta on virus yield, (2'-5')oligo(A) synthetase activation, H-2 antigen expression and proliferation of T lymphocytes have been investigated. Under the culture conditions used, vesicular stomatitis virus or Semliki Forest virus replication in T cells was not impaired by the addition of IFN-gamma, whereas it was completely inhibited by the addition of IFN-alpha/beta. In contrast, B cell lines, macrophage-transformed cell lines and fibroblasts were fully protected by both IFN-gamma as well as IFN-alpha/beta following virus infection. The lack of sensitivity of T lymphocytes to the antiviral effects of IFN-gamma was not due to absence of specific membrane receptors, since in saturation binding experiments with 125I-labeled murine IFN-gamma most T cell lines displayed a number of binding sites and a degree of affinity comparable to those found on B cells, which are fully sensitive to IFN-gamma antiviral activity. Analysis of IFN-induced dsRNA-dependent (2'-5')oligo(A) synthetase activity, one of the biochemical markers for cellular responses to IFN, showed that it was not induced in T lymphocytes after IFN-gamma treatment, whereas IFN-alpha/beta induced high levels. Both IFN-gamma and IFN-alpha/beta enhanced H-2 antigen expression on T cells as well as on cells of different histological type. Moreover, when IFN-gamma was tested for its antiproliferative activity on T cells, it was found to consistently potentiate the response of these cells to mitogens or growth factors, rather than inhibit their proliferation. Taken as a whole these results suggest that on T lymphocytes IFN-gamma should not be regarded as an antiviral agent, but rather as a modulator of T cell growth and functional differentiation, transducing intracellular signals dissimilar to those observed with target cells of different origin.
Landolfo
S
S
Department of Microbiology, Medical School, University of Torino, Italy.
Gariglio
M
M
Gribaudo
G
G
Jemma
C
C
Giovarelli
M
M
Cavallo
G
G
D015088:2',5'-Oligoadenylate Synthetase / Q000096:biosynthesis; D000818:Animals; D003208:Concanavalin A / Q000494:pharmacology; D006183:H-2 Antigens / Q000032:analysis; D007370:Interferon Type I / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D012672:Semliki forest virus / Q000254:growth & development; D013601:T-Lymphocytes / Q000166:cytology* / Q000382:microbiology; D014721:Vesicular stomatitis Indiana virus / Q000254:growth & development; D014762:Viral Interference
D006183:H-2 Antigens; D007370:Interferon Type I; D003208:Concanavalin A; D007371:Interferon-gamma; D015088:2',5'-Oligoadenylate Synthetase