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The data presented confirm previous evidence of delayed hypersensitivity in mice following infection with Junin virus. Adaptive transfer of sensitized cells from adult mice which had received 5 Junin virus injections into preinfected newborn mice shortened their survival by 72 hours. It was clear, however, that the development of the immunological mechanism in adult mice occurred under certain conditions. This evidence was confirmed by the observations that the induction of cell-mediated immunity and the response of sensitized lymphocytes to viral antigens appeared to be related to multiple injections of the virus. On the other hand, the sensitized cells were present in adult mice by day 9 and vanished 60 days after the infection. These results revealed the difference between the lymphoid cells from adult mice in the early and the late stages of immunity. The implications of these results in the development of the fatal neurological disease induced by the Junin virus in newborn mice are discussed.

Several aspects of the appearance and development of delayed hypersensitivity in mice infected with Junin virus are described. The results obtained showed that the development of the immunological mechanisms occurs irrespective of age. Spleen cells of donor mice inoculated with one i.p. dose of Junin virus had a poor cytotoxic activity, as demonstrated by 51Cr release and adoptive immunity procedures. Spleen cells treated with anti-theta serum and complement did not strikingly affect the development of Junin virus disease in mice. This demonstrated the capacity of T lymphocytes to influence the course of the viral infection of newborn mice adoptively transferred with immune spleen cells. No difference were detected in the virus titer in the brains of transferred and control animals, this fact suggests that immune T lymphocytes are not involved in Junín virus clearance.

The object of this paper was to determine the influence of cyclophosphamide immunosuppression on the mortality of 40-45 day old Balb/c mice infected intracerebrally with a pathogenic strain of Junin virus, using different administration schedules. Up to 200 mg/kg of cyclophosphamide were not toxic. Results show that, unlike in other experimental models, three or four 50 mg/kg cyclophosphamide doses given both before and after viral infection were required to break-down resistance to Junin virus (90-96.5% mortality vs. 8% in controls). Taking into account the effect of cyclophosphamide on the cell populations involved in the immune response, causes likely to lead to the greater susceptibility of the suppressed adult mouse to Junin virus are discussed.

Delayed-type-hypersensitivity (DTH) response "in vivo" is commonly evaluated by the footpad swelling test (FPST). High doses of Sheep Red Blood Cells (SRBC) are known to produce negligible DTH, while low doses lead to optimal sensitization. As expected FPST values obtained in Balb/c mice using 10(6) or 10(8) SRBC as sensitizing doses, showed that in 9 out of 10 batches from individual rams, the former dose resulted in higher values than the latter. However, only 3 out of the above 9 exhibited statistically significant differences between immunizing doses (Table 1). Therefore, in our hands, the accuracy of FPST is highly dependent on the SRBC source. We suggest the need of testing individual SRBC batches at both dilutions before use.

Tacaribe virus is the member most closely related to Junín virus within the Tacaribe complex. It has been demonstrated that both viruses are indistinguishable by complement-fixation, due to the high cross-reactivity. However, adult guinea pigs are highly sensitive to infection with the XJ pathogenic strain of Junín virus whereas Tacaribe virus is nonpathogenic for this species. Furthermore this last virus protects them against Junín virus. The XJ strain reduces the immune response of guinea pigs to many antigens. Both the humoral response and the hypersensitivity of the Arthus type have been reduced in infected animals. Considering that Tacaribe virus could be used as vaccine antigen, the purpose of the present study was to investigate the effect of Tacaribe infection on the immune system of guinea pigs. The data reported here supports earlier findings showing that the XJ strain of Junín virus suppresses humoral immune response as indicated by lower precipitating antibody titers to ovoalbumin (which contributed to milder Arthus cutaneous reactivity) and a significant depression of plaque-forming cells to sheep erythrocytes. In contrast, Tacaribe-infected guinea pigs did not show detectable immunosuppression employing the same models. Similar results were found when the cell-mediated immunity was investigated. Tacaribe-infected guinea pigs had a normal immune response to contact sensitivity to 2-4 dinitro-1-fluorobenzene as demonstrated by measuring ear swelling and unmodified tuberculin reaction, after injection with complete Freund's adjuvant. Our results and those of previous investigations justify the consideration of Tacaribe immunization as an approach to the prophylaxis of Argentine Hemorrhagic Fever.

As previously postulated, the pathological changes which develop in 1-4 day old mice after intracerebral inoculation of 1-1000 DL50 of Junín virus prototype strain (XJ), was designated as experimental hemorrhagic fever of the mouse EHFm. In this paper, virus distribution, hematological alterations, interferon and circulating antibody responses are described. A mortality of 93.45% occurred between 9 and 20 days post-infection (p.i.), with 81.6% of death occurring between 11 and 18 days p.i. This last period can be considered to be the critical period of the disease. The study of virus distribution shows that the brain, where the virus was inoculated, was the only place where virus could be detected 48 hs, p.i. Four days p.i., the titer in the brain increased remarkably and virus was detected in the blood. Virus, within the same values, could be isolated up to the 10th. day. Invasion of liver and spleen occurred on the 10th. and 15th. days p.i., respectively (Fig. 1). The onset of clinical symptoms coincided with widespread disemination of the virus. CF antibodies were found only 15 days p.i., with a titer of 1/64. Neutralizing antibodies remained below detection levels during the whole experiment (Fig. 1). Surviving mice (6.3%) had high circulating antibody titers 40 days p.i. This result would indicate that the morobidity of EHFm is aproximately 100% (Table 1). Poor interferon response was registered in all the organs examined, indicating a low intereron producing ability for Junin virus6. Total leukocytes and lymphocyte counts showed a slight tendecy to drop, although the values were within normal range during the first ten days (Table 2, Fig 1). On day 14 p.i., a statistically significant decrease (p less than 0.001) was found. This leuko-lymphopaenia continued until death of the animals. It is expected that the data presente here would contribute to a better understanding of the Junin virus infection in the newborn mouse, the experimental animal used.