In vitro cellular and cytokine responses to mycobacterial antigens: application to diagnosis of tuberculosis infection and assessment of response to mycobacterial vaccines.

Abstract

Mycobacterial infection leads to the development of specific cell-mediated immune responses that have been measured clinically by assessing delayed-type hypersensitivity with Mantoux skin testing. Several characteristics of Mantoux skin testing for tuberculosis infection can make the procedure inaccurate, inconvenient, and sometimes misleading. It is also a poor predictor of immunity to tuberculosis in bacille Calmette-Gúerin vaccinees, yet decisions to revaccinate often are based on skin test responses after initial immunization. Skin testing with other mycobacterial antigens has similar limitations. In vitro assessment of cellular immunity to mycobacteria offers multiple, potential advantages over skin testing and has become technically feasible in recent years. Measurement of the effector functions that comprise cell-mediated immunity (eg, cytokine secretion and cytotoxicity) rather than cutaneous delayed-type hypersensitivity responses is more likely to reflect meaningfully specific mycobacterial immunity and, therefore, provide a means for determining mycobacterial immunity after immunization. Eliminating the variability in placement and interpretation inherent in skin testing could provide a more stable foundation for comparative studies in populations and improve decision making for individuals. Finally, in vitro testing permits the use of discrete mycobacterial antigens instead of crude protein preparations, allowing greater specificity in the detection of infection as well as assessment of responses to defined candidate vaccine antigens. Several studies have compared skin testing with in vitro proliferation of lymphocytes stimulated by mycobacterial antigens for the detection of Mycobacterium tuberculosis infection. Preliminary veterinary and human studies suggest that in vitro assessment of gamma-interferon production in response to mycobacterial antigens can be used to detect prior infection with organisms of the M tuberculosis complex. Streamlined techniques for in vitro testing of cellular immunity may allow its practical adoption in the clinical setting and lead to its use as a replacement for Mantoux skin testing.