The inability of most untreated patients with
Kala-azar to control their visceral
infections with Leishmania donovani has been attributed to a defective cell-mediated immune response to leishmanial
antigens. We examined the in vitro response of T cells, including Leu-2+-depleted T cell populations, to determine whether unresponsiveness could be reversed. These studies on patients with
visceral leishmaniasis in Bihar, north India, support previous observations regarding T cell unresponsiveness in patients with active disease: it is profound, it is specific, and it is reversible after successful
chemotherapy. However, these studies also indicate that the specific unresponsiveness cannot be reversed by depletion of "suppressor" Leu-2+ T lymphocytes, nor by the addition of exogenously supplied human IL 2 to the cultures. One interpretation of these results is that in active cases of
Kala-azar, there is an absence of Leishmania-specific T cells in the periphery. The possibility that reactive cells can be found in situ cannot be excluded. The observation that 13 of 25 family members of active cases were able respond to L. donovani in vitro or by skin testing suggests that the frequency of
infection within an endemic area in Bihar is very high, and that assays for T cell responsiveness are far better epidemiologic tools for the detection of
asymptomatic infection than is ELISA. Identification of such an exposed,
Kala-azar-resistant population will be required to study host factors which influence the development of disease in infected individuals.