Evidence for an alpha/beta T cell-independent mechanism of resistance to mycobacteria. Bacillus-Calmette-Guerin causes progressive infection in severe combined immunodeficient mice, but not in nude mice or in mice depleted of CD4+ and CD8+ T cells.

Abstract

SummaryDepleting thymectomized mice of CD4 + T cells, or CD4 + plus CD8 + T cells, rendered them incapable of resolving Bacillus-Calmette-Guerin (BCG) infection in their livers, spleens, kidneys, and lungs. However, it did not render them incapable of stabilizing infection in the latter three organs after an initial period of BCG growth. Athymic nude mice showed a similar capacity to control BCG growth in these organs after a certain stage of infection. In contrast, congenitally severe combined immunodeficient (SCID) mice appeared to offer no resistance to BCG infection, in that the organism grew progressively in all organs of these mice and was lethal for them beginning on day 55 of infection. The results suggest that, although CD4 + T cells are important for resolving BCG infection, an odB T cell-independent mechanism of resistance can be acquired at 2-3 wk of infection that is capable of inhibiting further BCG growth in all organs except the lungs. Because this mechanism is absent from SCID mice, it is likely that it depends on the functions of 3~/~ T cells, B cells, or both types of cells. In keeping with this possibility is the additional finding that SCID mice engrafted with lymph node cells depleted of CD4 + or CD8 + T cells were capable of expressing an appreciable level of resistance against BCG infection.I t is generally believed, on the basis of results obtained from adoptive immunization and T cell depletion studies, that immunity to infection with mycobacteria is mediated by T cells. It has been known for some time, for example, that mice in the process of resolving BCG infection acquire T cells that are capable, on passive transfer, of conferring increased antimycobacterial resistance on naive recipient mice (1, 2). More recently, experiments with mice depleted of T cell subsets have shown that depletion of CD4 + T cells, but not of CD8 + T cells, results in a reduced capacity to resolve BCG infection (3) and to defend against infection with Mycobacteriura tuberculosis (4). However, in the case of BCG infection, the same T cell depletion studies (3) revealed that the absence of CD4 + , or both T cell subsets, did not leave mice completely defensdess against infection. On the contrary, mice so depleted showed a surprising capacity to halt progressive growth of BCG after a certain stage of infection. Therefore, the interpretation that CD4 + T ceils are pivotal for resistance to BCG infection is not supported by the evidence. This paper will show that mice depleted of CD4 + plus CD8 + T ceils, and athymic nude mice, can acquire the ability to stabilize BCG infection after 2-3 wk of BCG growth. It will show, in addition, that SCID mice permit progressive BCG growth in all organs and begin dying of infection from day 55 on, but not if they are engrafted with coisogenic lymph node cells depleted of CD4 + or CD8 + T ceils. Therefore, acquired resistance to BCG infection is partly dependent on a mechanism that is independent of CD4 + and CD8 + T cells. Materials and MethodsMice. B6D2FI (C57BL/6 x DBA/2) mi...

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