Anne O'Garra", Kenneth Murphyb aDNAX Research Institute, Palo Alto, Calif.; b Department of Pathology, Washington University, St. Louis, Mo., USA The development of distinct subsets of CD4+ T cells during an immune response, distinguished by their ability to produce discrete patterns of cytokines, can determine whether an infectious organism is eradicated or is able to chronically colonize the host [1]. Thl cells producing IFN-y and lymphotoxin [2, 3], mediate cell-mediated immune responses, important for the clearance of many infectious organisms [1, 4-6], but have also been implicated in the immunopathology resulting from organ-specific autoimmmune diseases [7-10]. Th2 cells, producing cytokines such as IL-4, IL-5, IL-10 and IL-13 [3, 11, 12], were originally defined as predominant helpers of B-cell responses, and are now clearly implicated in allergic responses [12-15], by their activation of mast cells and eosinophils. The ability of cytokines such as IL-10 and IL-4 to inhibit inflammatory as well as Thl-type cell-mediated immune responses [16-19] may in part explain why cell-mediated and humoral immune responses were often observed to be mutually exclusive [20-22], and implicates the Th2 subset as important regulators of cell-mediated immunity. Although such polarized populations of Thl-and Th2-type T cells were originally difficult to observe in human systems, it is now clear that they can be isolated from peripheral blood and draining lymph nodes during chronic infectious diseases and allergy [12-15, 23-28]. This is in keeping with the fact that mouse Thl and Th2 clones have been generally obtained from hyperimmunized mice [2]. Helper T cells producing cytokines typical of both Thl and Th2 clones have also been described in both murine and human systems [1, 3, 12, 29-33]. These have been called ThO cells, and may be precursors of the polarized Thl-and Th2-type phenotypes [34]. Alternatively, ThO cells may represent a separate, stably differentiated population under some conditions.

It is possible that ThO cells are instrumental in eliminating some pathogens, where the correct balance of cell-mediated and humoral immunity can clear the organism with a minimum of immunopathology. Alternatively, in many chronic conditions polarized Thl-or Th2-type immune responses emerge that are mutually exclusive, perhaps in part because of counter-inhibitory effects of cytokines on the reciprocal subsets [16-19, 35, 36].