IntroductionDe novo T-cell generation requires a functional thymus. 1 The current paradigm is that the human T-cell repertoire is established during late fetal development and that, by the time of birth, thymectomy does not cause immediate immunodeficiency. 2,3 Thymic epithelial space-the component of the thymus relevant for T-cell production and selectioninvolutes rapidly after birth. Thymic involution starts at the age of 1 year and continues with a yearly loss of 3%. 4,5 The peripheral T-cell compartment is under homeostatic control 6 ; with the reduction in thymopoietic capacity, alternative mechanisms of T-cell generation are necessary to prevent lymphopenia. Autoproliferation of postthymic T cells, particularly those in the memory compartment, is now accepted as a mechanism of T-cell production. 7,8 With advancing age, a shift occurs from efficient thymic lymphopoiesis to T-cell generation through peripheral replication; however, both mechanisms likely coexist during adult life. Age-related loss of thymic function is not the only condition that necessitates alternative means of repopulating the T-cell compartment. A number of clinical conditions, including chemotherapy, bone marrow transplantation, and infection with human immunodeficiency virus, are associated with T-cell depletion and the subsequent need to regenerate T cells despite limited thymopoietic capability. Evidence shows that recovery of peripheral T-cell numbers after chemotherapy is from thymic sources in children younger than 18 years of age. 7 In adults, thymopoiesis may still contribute to some degree, but replication of peripheral T cells becomes the dominant mechanism of filling the pool. It is obvious that the proliferation of postthymic T cells, especially when not entirely random, can have profound consequences on the composition of the T-cell repertoire. 9,10 What precisely these consequences are for immunocompetence is not understood.Functionality of the immune system is tightly linked to the receptor diversity of the T-cell pool. 11,12 Obviously, a large spectrum of T-cell receptors (TCRs) increases the chances of recognizing invading microorganisms. Thymopoiesis, the single mechanism of creating novel T cells, should be the key factor in determining immunocompetence. Young adults carry approximately 2 ϫ 10 11 CD4 ϩ T cells and approximately 1 ϫ 10 11 CD8 ϩ T cells. 13,14 The highest degree of diversity would be obtained if each naive T cell in the pool had a unique TCR. However, such a high degree of diversity might not be advantageous because it would decrease the probability of antigen recognition at a given tissue site. Instead, a minimal clonal size for each naive T-cell specificity is required to increase the chance for a T cell to encounter antigen and to mount a defensive response. Generation of a minimal clonal size requires that T cells selected in the thymus undergo intrathymic or postthymic proliferation.Arstila et al 15 have estimated the clonal size of naive T cells in adult humans. They measured an average diversity ...