Synergy between Th1 and Th2 responses during Mycobacterium tuberculosis infection: A review of current understanding

Induction of Th1 (cell-mediated) immunity and associated production of IFN-gamma by CD4+ T cells has been widely used as a marker of protective immunity against tuberculosis (TB). This is based on two assumptions. The first is the widely accepted view that Mycobacterium tuberculosis (Mtb), the causative agent of TB is an obligate intracellular pathogen, and the second is based on the Th1/Th2 paradigm, which posits that polarization of CD4+ T cells into type1 (cell-mediated) and type 2 (humoral) is central for proper induction of protective immunity against pathogens. However, almost all licensed vaccines currently in use are primarily anti-body based whether intracellular or extra-cellular. In addition, converging data from both animal models and humans indicate that the production of IFN-gamma alone is not sufficient to confer protection against TB. In addition, a substantial body of the literature suggests that, in addition to Th1 cells, antibody classes and sub-classes are protective against TB. In a recent study, we have shown that there is a synergy between IFN-gamma (cell-mediated) and IgA (humoral) in human population in an endemic setting. In this review, current data from both animal and human studies that support mixed Th1 and Th2 responses that are protective against Mtb and other pathogens are presented.