Co-stimulatory signals increase the reactivity of gammadelta T cells towards mycobacterial antigens.

Although it has been shown that gammadelta T lymphocytes are able to react with different cell-associated or soluble antigens, the immune repertoire of these cells appears to be skewed to the recognition of mycobacterial antigens. We have studied the number and reactivity of gammadelta T cells towards several mycobacterial antigens in patients with tuberculosis and leprosy, as well as their healthy contacts and control individuals. We found an increased number of Vdelta2+ cells in healthy contacts (PPD+ and lepromin+) and tuberculoid leprosy patients. The gammadelta T cells from lepromatous leprosy showed a decreased response to all antigens tested, but some of these patients exhibited a significant response to the 30-kD glycoprotein of Mycobacterium tuberculosis. Interestingly, the reactivity of gammadelta T cells against mycobacterial antigens was significantly increased by costimulatory signals generated through CD7, LFA-1, CD50 and CD69 in all groups. However, signalling through CD69 did not enhance the responsiveness of gammadelta lymphocytes from lepromatous patients. On the other hand, the in vitro blockade of IL-10 with a specific antibody enhanced the cell proliferation of gammadelta lymphocytes from lepromatous leprosy patients, whereas exogenous IL-10 had an opposite effect in most individuals studied. These results suggest the potential role of different cell membrane receptors in the regulation of gammadelta T cell proliferation induced by mycobacteria, as well as the possible involvement of IL-10 in this phenomenon.

Human CD4-CD8- alpha beta + T-cell receptor T cells recognize different mycobacteria strains in the context of CD1b.

Double-negative alpha beta+ T-cell receptor (TCR) human T cells have been reported to recognize antigen in the context of the HLA class I-like (Ib) CD1 complex. In particular, the CD1b molecule has been shown to act as the element of genetic restriction for antigens derived from Mycobacterium tuberculosis. The stenotopic nature of these major histocompatibility complex (MHC) class Ib molecules raised the question of whether the antigenic moiety recognized by CD4-CD8- alpha beta+ TCR T cells was shared by different mycobacteria. We demonstrate here that a CD4-CD8- alpha beta+ TCR T-cell line and three clones raised against M. tuberculosis proliferated following stimulation with soluble extracts from organisms of the M. tuberculosis complex, M. leprae and 10 out of 16 tested isolates of M. avium complex; however, four species of weakly or non-pathogenic mycobacteria were not stimulatory. Furthermore, the M. tuberculosis soluble extract (MTSE)-derived, recognized antigenic moiety proved to be proteinase K resistant and to have a molecular weight greater than 5000 MW, thus it differed from the reported antigenic moiety, recognized by CD4-CD8- gamma delta+ TCR cells. Our results suggest that a common antigenic moiety, presented by CD1b molecules to CD4-CD8- alpha beta+ TCR T cells, is shared by many mycobacterial species. Therefore they raise interest in the question of whether CD4-CD8- alpha beta+ TCR T cells, elicited by M. tuberculosis, may play a role in the natural history of other mycobacterial infections.

Raised agalactosyl IgG and antimycobacterial humoral immunity in Takayasu's arteritis.

OBJECTIVE: Takayasu's arteritis is an inflammatory occlusive disease of the aorta and its main branches of unknown etiology. Some suggested causes include inapparent infection with Mycobacterium tuberculosis, or autoimmunity evoked by this organism. We have therefore sought links with mycobacterial disease. METHODS: We assayed the % agalactosyl IgG, antibody to a tuberculosis-specific 38 kDa protein, and antibody to the mycobacterial 65 kDa heat shock protein (HSP), in patients with active or inactive Takayasu's arteritis, in whom the diagnosis of tuberculosis was excluded. The results were compared with findings in tuberculosis (positive controls), normal donors and patients with Wegener's granulomatosis. RESULTS: The % agalactosyl IgG in patients with active arteritis was in the range previously seen only in rheumatoid arthritis, Crohn's disease, and the mycobacterioses. Similarly, significantly raised antibody to the purified 38-kDa protein of M. tuberculosis, and to the 65-kDa HSP of M. leprae, was found in 78% of patients with Takayasu's arteritis, and the levels were higher in those with active disease. CONCLUSION: These results suggest that Takayasu's arteritis particularly clearly illustrates the occasional relationship between mycobacteria and diseases of superficially autoimmune pathogenesis.

High antibody levels to the mycobacterial fibronectin-binding antigen of 30-31 kD in tuberculosis and lepromatous leprosy.

Immunoblot assays showed that mycobacterial fibronectin-binding antigens are important targets of the humoral immune response in tuberculosis and leprosy. Using culture filtrate antigens of Mycobacterium tuberculosis, strong reactivity with the fibronectin-binding of 30-31 kD (Fn 30-31) was demonstrated in 55.9% of tuberculosis sera and in 56.5% of lepromatous leprosy sera. Sera from patients with tuberculoid leprosy and control sera gave very weak binding. Reactivity of tuberculosis and lepromatous leprosy sera with the fibronectin-binding antigen of 58-60 kD (Fn 58-60) was less conspicuous. The ability to react with fibronectin of the antigens of 58-60 and 30-31 kD was demonstrated by parallel labelling with a fibronectin-biotin conjugate. Fn 30-31 was purified to homogeneity by a two-step procedure and used for ELISA. Positive titres were found in 63% out of 65 tuberculosis sera and in 60.5% out of 43 lepromatous leprosy sera. Antibody titres in lepromatous leprosy sera were higher than in tuberculosis sera. Our observations indicate indirectly that M. leprae possess a highly immunogenic molecule homologous to M. tuberculosis Fn 30-31, which elicits a high antibody response in lepromatous leprosy but not in tuberculoid leprosy. In this investigation, direct evidence for the presence of this antigen in M. leprae was obtained by immunochemistry of lepromatous leprosy lesions with a monospecific antibody raised against M. tuberculosis Fn 30-31.