Defective antigen processing associated with familial disseminated mycobacteriosis.
To gain insights into a possible immune defect predisposing to disseminated mycobacteria infection, we studied three of six surviving children with disseminated Mycobacterium avium complex infection, who had no recognized form of immunodeficiency. We used mycobacteria isolated from the patients and diphtheria, tetanus and pertussis vaccine (DTP) to study antigen-specific T lymphocyte responses. We observed that interferon-gamma (IFN-gamma) production by T cells in response to antigens (both mycobacteria and DTP) in these patients with disseminated infection was greatly impaired. This defect did not seem to be the result of T cell unresponsiveness, as phytohaemagglutinin (PHA) stimulation was able to induce high levels of IFN-gamma comparable to those seen in control patients with localized infection. Further experiments showed that peripheral blood mononuclear cells (PBMC) from patients with disseminated infection were able to present influenza haemagglutinin (HA) peptides to specific T cell clones. However, this ability was lost when the whole HA protein was used as source of antigen. Taken together, these observations support the notion that the primary immune defect in these patients with disseminated mycobacterial infection rests in the antigen-processing functions of their antigen-presenting cells (APC). These findings may provide clues to the wider problem of susceptibility to mycobacteria and other intracellular pathogens and have implications in designing therapy for these patients.
D'Souza
S
S
Department of Immunology, St Mary's Hospital Medical School, Imperial College of Science, Technology and Medicine, London, UK.
Levin
M
M
Faith
A
A
Yssel
H
H
Bennett
B
B
Lake
R A
RA
Brown
I N
IN
Lamb
J R
JR
D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000096:biosynthesis; D015707:HN Protein / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation; D015269:Mycobacterium avium Complex / Q000276:immunology*; D015270:Mycobacterium avium-intracellulare Infection / Q000209:etiology / Q000276:immunology*; D009975:Orthomyxoviridae / Q000276:immunology; D010835:Phytohemagglutinins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology
D000942:Antigens, Bacterial; D016207:Cytokines; D015707:HN Protein; D010835:Phytohemagglutinins; D007371:Interferon-gamma