Intrathymic ontogeny of the T cell receptor associated CD3 (T3) antigen

Intrathymic T cell maturation has been studied in great detail, yet much of this process remains controversial. One of the critical steps in thymocyte maturation is the surface expression of the T cell antigen receptor associated CD3 (T3) antigen. The expression and ultrastructural localization of this antigen was therefore studied in tissue sections of five human thymuses using the monoclonal antibody UCHT-1. Thymocytes were also independently categorized morphologically as small nonblastic, large blastic, or intermediate. CD3 positivity was identified in 89% of cortical thymocytes and 92% of medullary thymocytes. Of the CD3+ cells, staining was present in the perinuclear region in 48% of cortical thymocytes and in only 11% of medullary thymocytes. Surface membrane staining was present in 87% of CD3+ cortical thymocytes and 99% of CD3+ medullary thymocytes. Of the CD3+ cortical large blastic thymocytes, 97% had perinuclear staining, but only 31% had surface positivity. Conversely, 98% of CD3+ medullary large blastic thymocytes had surface staining, but only 17% had perinuclear positivity. Almost all cortical and medullary small nonblastic thymocytes had surface membrane CD3 positivity, whereas perinuclear positivity was rare in these cells. These data suggest that the most immature CD3+ thymocytes (the large blasts with perinuclear CD3 positivity only) are present almost exclusively in the cortex. Maturation defined by the loss of perinuclear CD3 positivity and the acquisition of surface CD3 also occurs in the cortex. The vast majority of medullary thymocytes have surface CD3 positivity only.