T cell reactivity to the purified mycobacterial antigens p65 and p70 in leprosy patients and their household contacts

Abstract

SUMMARYT cell reactivity to the 70 and 65 kD (p70 and p65) protein antigens derived from Mycobacterium bovis BCG strain was studied by measuring the proliferative responses of peripheral blood mononuclear cells from members ofan isolated Aboriginal eommunity resident in the Torres Straits islands. In tbe nine index leprosy cases the pattern of responsiveness to the purified antigens paralleled that to whole sonicates from M. leprae and BCG. In the 40 contacts of tbe index cases, a high correlation was observed between the responses to p70 and p65 as well as to the crude sonicates. Significant T cell responses to the purified antigens, as well as the erude sonicates, were obtained with cells from the majority of contacts. Limiting dilution analysis of precursor frequencies in tbe contacts confirmed the immunogenicity of the purified antigens and excluded both a mitogenie component and tbe presence of suppressor cells in those moderate or low responders whose blood contained sufficient precursors to be tested. p70 appeared to be more potent in stimulating a proliferative response than p65 at equivalent protein concentrations. No correlation between responder status to cither antigen and disease type was detected in families. These findings provide confirmation of the importance of p70 and p65 as major T cell immunogens in man and indicate that they are botb potential candidates for inclusion in a bivalent vaccine for leprosy and tuberculosis.

Lack of cytotoxic activity against Mycobacterium leprae 65-kD heat shock protein (hsp) in multibacillary leprosy patients

“…leprae hsp65. Many authors have observed, as in our study, that while cells from healthy contacts and PB patients proliferated against mycobacterial hsp65, most LL patients failed to respond to this protein fraction [11,[39][40][41]. These results are opposed to those of Mendez-Samperio et al [42], who observed higher responses in LL than in TT patients.…”

Cellular and humoral immune responses to recombinant 65-kD antigen of Mycobacterium leprae in leprosy patients and healthy controls

“…In vitro lymphoproliferative responses to rML65 were observed in a considerable proportion of tuberculoid leprosy patients, healthy contacts and non-contacts. A similar finding has been reported for the 65-kD antigen of BCG [17,18]. Compared with these reports, the proportion of responders to rML65 is low in our study, and this may quite well be due to the stringent criteria we have used for defining the positive response.…”

“…The mycobacterial 65-kD antigen has also been demonstrated to be a major T cell immunogen in mice [9,10]. Several studies have demonstrated the presence of T cells reactive to the mycobacterial 65-kD antigen in humans by deriving specific helper and cytotoxic T cell clones from leprosy and tuberculosis patients and healthy volunteers [11][12][13][14][15], However, population studies in leprosy patients and healthy endemic controls are required to evaluate the true immunological significance ofthe recombinant antigens [16], There are only a very few such studies on cellular and humoral immune responses to the mycobacterial 65-kD antigen [17][18][19][20][21], Further, both responses were not evaluated together in any of these investigations. Therefore, we studied the lymphoproliferative response and IgG and IgM antibody levels to the recombinant Myco.…”

Nerve and skin damage in leprosy is associated with increased intralesional heat shock protein

“…The localized accumulation of hsp70 could contribute to the immunopathology of leprosy reactions. Hsp70 from lysed cells may be presented via HLA class II molecules to an immune sy.stem already primed for recognition of the bacterial homologue [28], and may amplify or prolong the inflammatory response, while cytoplasmic hsp presented by HLA class I molecules could provide targets for potentially damaging cytolytic T cells. Hsp autoreaetive cytolytic T cells have been shown to recognize macrophages stressed in in vitro cell culture experiments, although this was mediated via hsp60 rather than hsp70 [29].…”