Correlation between cyclophosphamide-induced viral susceptibility and depletion of Junin virus-induced suppressor populations.
In contrast to lymphocytic choriomeningitis virus, another arenavirus, Junin virus (JV), the etiologic agent of Argentine hemorrhagic fever, when inoculated into suckling mice, induces lethal meningoencephalitis characterized by a delayed-type hypersensitivity (DTH)-like immune response. However, the adult BALB/c mouse is resistant to infection and no DTH reaction can be seen. This different viral sensitivity may be related to the development of an antigen non-specific DTH-suppressor cell pathway at work in the adult mouse. When the resistant mice are treated with cyclophosphamide (Cy) (50 mg/kg each dose) given at days -1,+1,+4 (zero: infection day), animals become susceptible and develop DTH reaction in brain that leads to death. We analyze the influence of the timing of Cy administration on the suppressor system developing after infection. It was found that Cy depletes the previously described JV-induced suppressor populations (Tsv) but a new suppressor cell (Tsv*) is disclosed bearing the Thy 1+ Ly1+2- phenotype which is unable to depress DTH in Cy-treated animals. With only two doses of Cy corresponding to days -1 and +1, the target of Tsv* cells is depleted but the third dose is still required to achieve full depletion of Tsv cells which are able to employ the Cy-resistant antigen-specific suppressor cells as targets. Since the Cy treatment is able to deplete the Tsv population together with the target of Tsv* cells, animals became unable to regulate lethal DTH reaction. Thus, a cellular explanation for an empirically established Cy schedule able to abrogate the adult mouse resistance to JV is proposed.
Campetella
O E
OE
Departamento de Microbiología, Facultad de Medicina, Universidad de Buenos Aires, Argentina.
Galassi
N V
NV
Barrios
H A
HA
D000818:Animals; D000833:Animals, Suckling; D006477:Arenaviruses, New World / Q000276:immunology*; D003520:Cyclophosphamide / Q000494:pharmacology*; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D004912:Erythrocytes / Q000276:immunology; D006478:Hemorrhagic Fever, American / Q000150:complications / Q000276:immunology*; D006968:Hypersensitivity, Delayed / Q000139:chemically induced / Q000209:etiology / Q000276:immunology*; D008212:Lymphocyte Depletion; D008590:Meningoencephalitis / Q000139:chemically induced / Q000209:etiology / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000166:cytology / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D003520:Cyclophosphamide