After earning a medical degree from the University of Lisbon, Benedita performed her PhD work with Maria de Sousa in Glasgow, where she explored the regulatory function of T lymphocytes in immune responses. She then moved to the Medical School of Nova University, Lisbon, where she was appointed Professor of Immunology. In these early days, Benedita hypothesized the existence of regulatory mechanisms that maintain lymphocyte numbers, laying down the foundations for her future work on T cell homeostasis.
In the 1980s, Benedita moved to the Necker–Enfants Malades Hospital in Paris, where she made major contributions to the understanding of T cell physiology. In her adopted city, Benedita interacted with phenomenal immunologists and postulated the existence of peripheral T cell tolerance mechanisms. At the time, the dominant theory indicated that T cell tolerance was solely defined in the thymus, during the differentiation of immature T cell precursors, but Benedita thought otherwise. As such, she joined forces with Harald von Boehmer at the Basel Institute of Immunology, in Switzerland, to investigate whether mature T cells can become tolerized in the periphery. In the early 1990s, the efforts of Benedita and Harald culminated with the demonstration that peripheral tolerance to self-antigens occurs through the elimination of self-reactive T cells and through T cell clonal anergy. This seminal work paved the way for multiple studies on peripheral T cell tolerance and had important implications for autoimmune disease research.