In vitro human lymphocyte responses to Cryptococcus neoformans. Evidence for primary and secondary responses in normals and infected subjects.

Abstract

Cryptococcus neoformans causes meningitis and disseminated infection in healthy individuals, but more commonly in hosts with defective immune responses. To study the role of immune lymphocytes in protection and recovery from this infection, in vitro lymphocyte proliferative responses to whole killed organisms were characterized in normal controls and in patients with cryptococcosis. Several differences were found between these two groups. All normal individuals were found to have significant proliferative responses to cryptococci in vitro; however, patients recovering from infection had accelerated and augmented responses. Patients' T cells, but not control T cells, were found to produce interleukin 2 (IL 2) during initial stimulation in vitro. After in vitro priming, mononuclear cells from normal controls rechallenged with cryptococci in vitro demonstrated accelerated kinetics and IL 2 production similar to that of cells from recovering patients. Proliferative responses in normals required T cells and antigen-presenting cells, and resulted in an increase in the proportion of T8+ and Tac+ cells in the responding population by the ninth day of primary stimulation. An increase in Tac+ cells, but not T8+ cells, was found by the fourth day of secondary stimulation. These results demonstrate in vivo acquisition of T cell responsiveness to the organism in this small group of recovering patients, and in vitro acquisition of T cell recognition of this antigen by normal T cells during primary stimulation. The data suggest that these responses represent in vitro priming to cryptococci and indicate a role for the T8+ lymphocyte subpopulation, both unusual findings for previously described in vitro responses to soluble antigens.