Loci controlling lymphocyte production of interferon c  after alloantigen stimulation in vitro and their co-localization  with genes controlling lymphocyte infiltration of tumors  and tumor susceptibility.
Low infiltration of lymphocytes into cancers is associated with poor prognosis, but the reasons why some patients exhibit a low and others a high infiltration of tumors are unknown. Previously we mapped four loci (Lynf1–Lynf4) controlling lymphocyte infiltration of mouse lung tumors. These loci do not encode any of the molecules that are involved in traffic of lymphocytes. Here we report a genetic relationship between these loci and the control of production of IFNγ in allogeneic mixed lymphocyte cultures (MLC). We found that IFNγ production by lymphocytes of O20/A mice is lower than by lymphocytes of OcB-9/Dem mice (both H2pz) stimulated in MLC by irradiated splenocytes of C57BL/10SnPh (H2b) or BALB/ cHeA (H2d) mice, or by ConA. IFNγ production in MLCs of individual (O20 9 OcB-9)F2mice stimulated by irradiated C57BL/10 splenocytes and genotyped for microsatellite markers revealed four IFNγ-controlling loci (Cypr4-Cypr7), each of which is closely linked with one of the four Lynf loci and with a cluster of susceptibility genes for different tumors. This suggests that inherited differences in certain lymphocyte responses may modify their propensity to infiltrate tumors and their capacity to affect tumor growth.
Lipoldová
Marie
M
Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Vídenká 1083, 14220 Prague 4, Czech Republic. lipoldova@img.cas.cz
Havelková
Helena
H
Badalova
Jana
J
Vojtísková
Jarmila
J
Quan
Lei
L
Krulova
Magdaléna
M
Sohrabi
Yahya
Y
Stassen
Alphons P
AP
Demant
Peter
P
D000818:Animals; D002874:Chromosome Mapping; D005260:Female; D056426:Genetic Loci; D007371:Interferon-gamma / Q000096:biosynthesis*; D007519:Isoantigens / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains
D007519:Isoantigens; D007371:Interferon-gamma