Relative Immunogenicity of Streptomycin-Sensitive and -Resistant Strains of BCG

Mycobacterium marinum has been recommended as a possible model of M. leprae for use in laboratory studies of antileprosy immunity. M. marinum introduced into the footpads of normal mice underwent a steady decline in viability, with less than 1% survival after a 30-day period. Small numbers of viable bacilli were recovered from the footpads of these mice up to 12 months later. Similarly, mice infected with M. simiae exhibited bacterial populations that persisted for up to 18 months with little change in viability. Injection of M. simiae into the footpads was followed by an extensive redistribution of the organisms in the tissues. Eventually, bacterial counts for footpads and draining lymph nodes stabilized, with small numbers of bacilli still present in the footpads 18 months later. Persistent growth, with little sign of any immune response, was also observed in mice infected with several strains of M. avium, as well as with one strain of M. intracellulare. Other strains of M. intracellulare, as well as M. vaccae and M. nonchromogenicum, failed to establish persistent infections in normal mice, regardless of whether they were introduced by an intravenous or subcutaneous (footpad) route. The relevance of these findings is discussed in relation to antileprosy immunity in experimental animals and in humans.

Section: Resultsmentioning

confidence: 96%

“…The fully grown culture was diluted with an equal volume of fresh MSTA and stored in 1-ml ampoules at -70°C (17). The viability of each suspension was determined by thawing the ampoules at 37°C, briefly homogenizing the suspension to break up the clumps, and plating suitable 10-fold Tween-saline dilutions on Middlebrook 7H10 agar (6,9).…”

Section: Methodsmentioning

confidence: 99%

Immune response to persistent mycobacterial infection in mice

Collins¹,

Morrison²,

Montalbine³

1978

“…They were fed sterile commercial mouse chow and acidified water ad lib. (6). Sham-thymectomized (XB) and normal age-matched controls were included in most of the studies (5).…”

Section: Methodsmentioning

confidence: 99%

“…Organisms. M. bovis (BCG Pasteur: TMC #1011) was grown in modified Santon's Tween albumin broth (8) incubated at 370C in roller tubes for 14 days and stored in 1-ml ampoules at -70'C, as described previously (6). When required, an ampoule was thawed at 370C, homogenized in an equal volume of fresh modified Santon Tween albumin, exposed for 3 a to sonic oscillation to break up the remaining clumps, diluted appropriately in Tween saline, and used to generate an aerosol of live BCG in a Middlebrook chamber (Tri-R Industries, New York, N.Y.), as described previously (18).…”

Section: Methodsmentioning

confidence: 99%

Restoration of T-cell responsiveness by thymosin: expression of anti-tuberculous immunity in mouse lungs

Collins¹,

Morrison²

1979

Specific pathogen-free, adult thymectomized, irradiated, and bone marrowreconstituted (THXB) B6D2 mice were infected aerogenically with 1 x 103 to 5 X 103 live BCG Pasteur. Seven days later a group of the mice was placed on a 14day regimen of 20 mg of calf thymosin per kg per day, and the growth of the BCG in the lungs, spleen, inguinal lymph node, bone marrow, and blood was determined for up to 90 days. The thymosin treatment was followed by a decline in the BCG counts for the lungs and spleens of the THXB mice, whereas the saline-treated controls showed no such decline with time. The thymosin-treated mice did not develop progressive BCG infections in the test lymph nodes or in the bone marrow, both of which became positive in the THXB mice. Spleen cells were harvested from thymosin-treated THXB donors, filtered through nylon wool, and infused three times into BCG-infected THXB recipients. The lung BCG counts declined approximately 10-fold by day 90 compared with THXB mice which received THXB spleen cells. The transferred immune response was only slightly smaller numerically than that seen in THXB mice infused with BCG-immune lymphocytes from normal donors. cellular deficiency. N. Engl.

“…However, not all living attenuated mycobacteria are capable of inducing significant levels of cell-mediated immunity (10,13). This inability on the part of the nonpersisting mycobacterial inoculum to sensitize the host occurs despite the presence of the relevant antigens in the bacterial cell (12). Active sensitization requires a persistent, metabolically active population of bacteria in the spleen or the draining lymph node (13).…”

Section: Downloaded Frommentioning

confidence: 99%

Delayed hypersensitivity responses in mice and guinea pigs to Mycobacterium leprae, Mycobacterium vaccae, and Mycobacterium nonchromogenicum cytoplasmic proteins

Watson

Morrison²,

Collins

1979

Antigenic relationships between Mycobacterium vaccae, M. nonchromogenicum, and M. leprae were examined in mice and guinea pigs injected with M. vaccae or M. nonchromogenicum suspensions. The growth of both organisms in outbred ICR and four inbred mouse strains was followed up to 30 days. M. nonchromogenicum persisted in the livers and spleens of the inbred mice substantially better than did the M. vaccae population in the same mouse strains. A translucent colony variant of M. vaccae isolated from the opossum survived in vivo better than the opaque colony isolated from opossums and cattle. Persistence of M. vaccae and M. nonchromogenicum was not markedly increased in T-celldepleted (nude) mice. Normal mice infected with increasing numbers of M. vaccae did not develop delayed-type hypersensitivity to the homologous M. vaccae cytoplasmic protein antigen. When heat-killed M. vaccae were incorporated into Freund adjuvant, both mice and guinea pigs developed delayed hypersensitivity to cytoplasmic antigens prepared from M. vaccae, M. nonchromogenicum, and M. keprae, but not to purified protein derivative. Both M. nonchromogenicum and M. vaccae vaccines cross-sensitized guinea pigs to the M. leprae cytoplasmic antigens.