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Presence of Host‐Reactive and MHC‐Restricted T Cells in a Transplanted Severe Combined Immunodeficient (SCID) Patient Suggest Positive Selection and Absence of Clonal Deletion

Mature T cells in the periphery are derived from progenitor cells that originate in the fetal liver or bone marrow and migrate to the thymus during ontogeny. These pre-T cells undergo a series of complex maturational events that result in the expression of clonotypic TCR's on these cells. During these maturation processes the T cells learn to distinguish self from non-self. The mechanisms of this selection that occurs in the thymus are incompletely understood. It is believed that T cells carrying aP T-cell receptors with potential to recognize foreign peptide sequences associated vnth self MHC are selected by interactions with self MHC antigens expressed on thymic cortical epithelial cells (Zinkernagel et al. 1978, Bevan & Fink 1978, Kruisbeek et al. 1985, Farr et al. 1986), while those able to recognize self peptide are eliminated when they interact with MHC on bone marrow-derived cells present in the thymic medulla (Jenkinson et al. 1985, Lo et al. 1986, von Boehmer & Schubiger 1984, Marrack et al. 1988). Besides clonal deletion, two other possible mechanisms for T-cell tolerance have been proposed: clonal anergy involving specific inactivation of self-reactive T cells (Nossal & Pike 1983, Rammensee et al. 1990), and suppression of self-reactive T cells by other T cells (Gershon & Kondo 1971). Elegant studies using transgenic mice