Changes in B and T lymphocytes associated with mycobacteria-induced protection of NOD mice from diabetes

Most female NOD mice spontaneously develop insulin-dependent diabetes mellitus (IDDM) after the 4th month of age. We have recently reported that infection of 2-month-old NOD mice with Mycobacterium avium prevents IDDM expression in these mice. We have searched here for changes in splenic lymphocytes that are associated with the effect of M. avium vaccination. Three experimental groups of female NOD mice were studied: (i) animals infected with 10B viable M. avium bacteria (mice that become protected from IDDM); (ii) mice inoculated with 10B heat-killed (HK) M. avium bacilli, and (iii) untreated age-matched NOD mice. Similar treatments were given to mice of the NON strain which are related to NOD mice but do not develop IDDM. Flow cytometry was used to compare M. avium-infected, HK M. avium inoculated and untreated NOD and NON mice with regard to subpopulations of splenic lymphocytes bearing the surface antigens CD3, CD4, CD8, IgM and B220. We found that M. avium infection of NOD mice caused a sustained enhancement in T cells that was due to an early and transient increase in CD8+ T cells (detected at day 7 of infection). This was followed by marked augmentation in the number of CD4+ T cells at days 14 and 30. There was also elevation in B220+ B cells at days 14 and 30, and of IgM+ B cells at day 30 of infection. Inoculation of NOD mice with HK mycobacteria, which did not prevent IDDM, failed to produce significant changes in the number of T and B cells. No significant enhancement in T and B cells was observed in NON mice that were injected with either viable or HK M. avium bacilli. In NOD mice that reached 16 months of age because of being protected from IDDM (due to the M. avium infection) there was an increase in B220+ B cells. We conclude that: (i) M. avium-induced protection of NOD mice from diabetes depends on the viability of the bacteria; (ii) the protective effect of the infection is associated with an early and marked increase in helper T cells and with a smaller elevation in B cells; (iii) elevation in B cells, but not in T cells, is associated with long term mycobacteria-induced protection of NOD mice from IDDM.