Cytokine transcripts in pediatric tuberculosis: a study with bronchoalveolar cells.

Pediatric tuberculosis (TB) differs from adult TB in many features. To date, cytokine expression has not been studied in children with TB. The relative amounts of the various cytokines released at the site of infection may be important determinants of TB disease development and pathology. We determined cytokine transcripts in bronchoalveolar cells (BACs) recovered from 9 children presenting with TB and from 9 children with pulmonary diseases other than TB. An RT-PCR-based method was developed to quantify the mRNAs encoding six cytokines (IFN- gamma, IL-12, TNF- alpha, IL-10, IL-4, TGF- beta 1) known to play key roles in mycobacterial infections. Expression of mRNA encoding TGF- beta, TNF- alpha and IFN- gamma was statistically significantly higher in BACs from children with TB than in BACs from children with other pulmonary diseases; whereas the levels of mRNA transcription for TGF- beta is high, the levels of mRNA transcription for IFN- gamma and TNF- alpha remain low. All children had low levels of mRNA for IL-12(p40). IL-4 was barely detectable in all cases. Children with miliary TB had high levels of IL-10 transcripts and low levels of mRNA encoding TGF- beta. The immunosuppressive cytokines TGF- beta and IL-10, are overproduced in children with non-miliary TB and miliary TB respectively and are probably involved in the progression of the disease. These data suggest that Th1 responses are reduced in children with TB.

Mycobacterium bovis BCG priming induces a strong potentiation of the antibody response induced by recombinant BCG expressing a foreign antigen.

Several recent studies have demonstrated that strong cellular or humoral immune responses can be induced against foreign antigens expressed by recombinant Mycobacterium bovis BCG. It has therefore been suggested that BCG could represent one of the best candidate vectors for live recombinant vaccines. However, a large percentage of the human population has been immunized by BCG, and this priming could modify the immune response to future recombinant BCG vaccines. In the present study, we have therefore compared the immune responses induced in naive and BCG-primed mice by two recombinant BCG vaccines expressing either beta-galactosidase or human immunodeficiency virus type 1 Nef antigens. Our results demonstrated that BCG priming limits the growth of recombinant BCG in mouse spleen or lymph nodes. This reduction in BCG growth was associated with decreased proliferative responses against Nef or beta-galactosidase antigens. This suppression, however, never exceeded 50%. Interestingly, in contrast to these reduced T-cell responses, BCG-primed mice developed high levels of anti-beta-galactosidase antibodies after immunization with recombinant BCG expressing this antigen. This stimulation of antibody responses was not due to polyclonal stimulation or to a nonspecific adjuvant effect of BCG. The isotypic patterns of anti-beta-galactosidase antibody responses induced by the recombinant BCG were similar in naive and BCG-primed mice. These results indicate that priming with BCG will not be a limitation for the use of recombinant BCG vaccines in humans.