Antiviral immune responses of lymphocytic choriomeningitis virus-infected mice lacking CD8+ T lymphocytes because of disruption of the beta 2-microglobulin gene

F Lehmann-Grube, J Löhler, O Utermöhlen, C Gegin
1993 Journal of Virology  
Mice infected intracerebrally with lymphocytic choriomeningitis virus (LCM virus) develop a characteristic central nervous system disease and usually die. If the intravenous or intraperitoneal route is used, the infection leads to less severe clinical signs and the virus is eliminated. Illness and virus clearance are immunological phenomena, which are assumed to be caused exclusively by CD8+ T lymphocytes. In contrast, of the two phases of a delayed-type hypersensitivity reaction caused by
more » ... lation of the virus into the mouse's foot, only the first is mediated by CD8+ cells, whereas the second is mediated by CD4+ cells. We have examined LCM virus-specific immune responses in mice devoid of CD8+ T lymphocytes as a result of disruption of the 132-microglobulin gene. As expected, the virus persisted but footpad swelling did not occur, although intracerebral infection resulted in CD4+ T-lymphocyte-mediated illness and antiviral antibodies were produced. Different results had been obtained by Fung-Leung et al. (W.-P. Fung-Leung, T. M. Kundig, R. M. Zinkernagel, and T. W. Mak, J. Exp. Med. 174:1425Med. 174: -1429Med. 174: , 1991, who, in essentially identical experiments but with mice lacking CD8+ T lymphocytes as a result of disruption of the Lyt-2-encoding gene, recorded control of the infection and development of a local delayed-type hypersensitivity reaction. We consider these differences important, because they provide us with clues that may help to understand the mode of action of the CD8+ T cells in cell-mediated antiviral immunity. Mass. They were specific pathogen free on receipt and were maintained and bred by us under strict barrier conditions. For the experiments, male and female mice aged 8 to 16 weeks were used. Virus. The WE strain LCM virus used here (51) is identical with the one used by . Presumably, the same is true with respect to strain Armstrong, although its origin is uncertain (26). Both viruses were propagated in L (NCTC clone 929) cells and quantitated as PFU in L cells (29) . Because mice are more susceptible than L-cell cultures and are less sensitive to nonviral constituents, the mouse assay was used for the detection of low levels of infectious virus in tissue homogenates. According to the results of comparative titrations in mice and L-cell cultures, the 50% infectious doses of WE and Armstrong strain LCM viruses determined in mice were, respectively, 10 and 40 times higher than the numbers of PFU determined in cells (25a). On this basis, PFU were converted to mouse infectious units (MIU) by multiplication by 10 and by 40. For determining infectious titers in tissues, weighed portions were homogenized with known volumes of balanced salt solution by using a mortar and pestle and some sand. L. monocytogenes. Listeria monocytogenes EGD (39) was supplied by H. Hahn, Institut fur Medizinische Mikrobiologie, Freie Universitat, Berlin, Germany. The bacteria were propagated in suspension and quantitated as CFU in tryptic soy broth and on tryptic soy agar (Difco Laboratories, Detroit, Mich.). Evaluation of lymphocytic choriomeningitis. Beginning on day 5 after intracerebral (i.c.) or intraperitoneal (i.p.) inoc-332
doi:10.1128/jvi.67.1.332-339.1993 fatcat:aaqrxqaeafhndfeut6spn6kzgu