Regulation of the human cellular immune response to Mycobacterium tuberculosis. The mechanism of selective depression of the response to PPD.
After infection with M. tuberculosis, about 5% of individuals develop progressive tuberculosis during the following two years and an additional 5% delayed reactivation. The genetic and acquired factors which place individuals at risk of tuberculosis are partly defined; however, the connection of the susceptibility to the host immune response is much less clear. Recent studies have examined the basis for the immunosuppression that is a concomitant of tuberculosis. Direct stimulation of monocytes primed during the course of tuberculous infection by mycobacterial peptides appears to be responsible for suppression of PPD-induced responses. Increased expression and release of interleukin-2 receptors and transforming growth-factor beta are associated with and may contribute to such suppression by monocytes. Additional studies have addressed the generation of immunity or immunosuppression. Ingestion of live M. tuberculosis by monocytes leads to selective expansion of gamma-delta T cells as opposed to CD4 lymphocytes. This may be relevant to the innate response to infection with M. tuberculosis as well as immunoregulatory circuits. Increased understanding of the basis for immunosuppression is of intrinsic interest as regards regulation of specific pathways of immune reactivity in an infectious disease of humans and may provide some insight into factors predisposing to tuberculosis.
Ellner
J J
JJ
Case Western Reserve University, Division of Infectious Diseases, University Hospitals, Cleveland, Ohio 44106.
D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology*; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D014374:Tuberculin Test / Q000592:standards*; D014376:Tuberculosis / Q000175:diagnosis / Q000276:immunology*