MYCOBACTERIAL INFECTIONS IN NUDE MICE

Abstract

T-cell-mediated and non T-cell-mediated granuloma formation and antibacterial resistance were examined using nude mice infected with mycobacteria.
Nude mice of BALB/c-background showed very low resistance to infections with a virulent and attenuated Mycobacterium bovis as well as to infection with M. avium in comparison with euthymic heterozygous littermate mice. This was evidenced by a shorter survival time, higher bacterial count and lesser number of granulomas in nude mice than in heterozygotes.
A low level of antimycobacterial resistance, however, seems to be operative in the liver and lymphoreticular organs of nude mice. After the virulent M. bovis-infection, the reticuloendothelia organs fell to exudative-necrotic lesions later than the other organs. Growth of attenuated strain BCG was suppressed in the RES organs revealing plateau in contrast to progressive increase in the lung and kidney. Such antimycobacterial resistance was less pronounced in nude mice maintained under germ-free condition than flora-bearing nude mice suggesting floral organisms play a roleprobably via macrophage activity for the non T-cell-mediated resistance.
Whether or not a T-cell independent immunological mechanism plays any role in the develop -ment of granulomas in nude mice after BCG infection or injection of killed organisms was pursued using nude mice rendered immunosuppressive against T independent antigen, Brucella abortus, by multiple injections of cyclophosphamide. The nude mice received such treatment still produced granulomas comparable in number and size to non-suppressed nude mice, and the fact indicates no participation of antibody-mediated mechanisms in the formation.
The low level of resistance and granuloma formation of nude mice in mycobacterial infections could be recovered, although never reached to the level of the heterozygotes, by transplantation with the thymus or T-cell-containing lymphoid cell suspensions from heterozygotes. Transfusion of spleen cells from intact mice possessing major histocompatibility antigen of the same halotype as to recipient BCG-infected nude mice (H-2d) produced hepatic granulomas while spleen cells from H-2-incompatible ones lacked such activity, and it suggests an H-2restricetd cell-interaction is operative in the T-cell mediated granuloma formation. This kind of cell transfer method seems to provide a useful procedure to investigate cellular interactions undergoing granuloma formation