In general, gamma interferon (IFN-␥)-producing CD4؉ Th1 cells are important for the immunological control of intracellular pathogens. We previously demonstrated an association between parasite-specific induction of IFN-␥ responses and resistance to the intracellular protozoan Trypanosoma cruzi. To investigate a potential causal relationship between Th1 responses and T. cruzi resistance, we studied the ability of Th1 cells to protect susceptible BALB/c mice against virulent parasite challenges. We developed immunization protocols capable of inducing polarized Th1 and Th2 responses in vivo. Induction of parasite-specific Th1 responses, but not Th2 responses, protected BALB/c mice against virulent T. cruzi challenges. We generated T. cruzi-specific CD4 ؉ Th1 and Th2 cell lines from BALB/c mice that were activated by infected macrophages to produce their corresponding cytokine response profiles. Th1 cells, but not Th2 cells, induced nitric oxide production and inhibited intracellular parasite replication in T. cruzi-infected macrophages. Despite the ability to inhibit parasite replication in vitro, Th1 cells alone could not adoptively transfer protection against T. cruzi to SCID mice. In addition, despite the fact that the adoptive transfer of CD4 ؉ T lymphocytes was shown to be necessary for the development of immunity protective against primary T. cruzi infection in our SCID mouse model, protective secondary effector functions could be transferred to SCID mice from memory-immune BALB/c mice in the absence of CD4 ؉ T lymphocytes. These results indicate that, although CD4 ؉ Th1 cells can directly inhibit intracellular parasite replication, a more important role for these cells in T. cruzi systemic immunity may be to provide helper activity for the development of other effector functions protective in vivo.

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In summary, these studies demonstrated that HIV-infected hemophiliac bone marrowderived nonadherent CD34 + SC were capable of differentiating and/or maturing into T cells when cocultured in a normal allogeneic thymic environment. Furthermore, the T cells derived from derived CD34 + SC were capable of differentiating into T cells when cocultured in a normal allogeneic thymic environment, proliferated maximally with APCs from the stem cell donor and were tolerant of thymic HLA class II antigens, and to a lesser degree to stem cell donor B cell HLA antigens.

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T cell immune function was further evaluated in cystic fibrosis (CF) patients. CF patients, regardless of severity of pulmonary disease or colonization with Pseudomonas aeruginosa, had lower percentages of T helper cells (p < 0.01) and decreased T helper function as demonstrated by diminished T help for control B cell pokeweed mitogen-stimulated IgG (p < 0.01) and IgM (p < 0.01) synthesis. Increased T suppressor function, measured by co-culture with control B and T cells, was noted in only 25% of CF patients. CF patients’ T cells exhibited decreased allogeneic T cell cytotoxicity compared to normal controls (p < 0.01). This study extends previous studies demonstrating decreased T cell functions in CF patients and indicates a specific decrease in T helper function.