Ontogeny of T-cell function: Alloreactivity appears earlier than reactivity against hapten-modified self and interleukin-2 production

The capacity to generate cytotoxic T cells (CTL) against allogeneic or hapten-modified syngeneic cells after in vitro sensitization was studied in C57BL/6J and CBA/H mice of different ages, beginning at 5 days of age. A differential maturation rate for allogeneic versus hapten-modified syngeneic CTL reactivity was observed in both strains, with alloreactivity appearing earlier than reactivity to hapten-modified self antigens. For example, in C57BL/6J mice, alloreactive CTLs were detected within the first week of life, reaching adult levels by the second-third week, while the response to modified-self appeared at the secon-third week and reached adult levels by the fourth-fifth week of life. Cross-reactive lysis of hapten-modified allogeneic targets followed the same maturation pattern as the modified-syngeneic response. The low CTL reactivity of 6-day-old spleens was not due to suppressor cells. Mixing Lyt-2− (Lyt-1+) and Lyt-2+ cells from 6-day-old and adult spleens showed that the main defect was in the T helper compartment. In addition, the capacity to produce interleukin-2 (IL-2) after mitogen or allogeneic stimulation was also defective in the young mice, appearing approximately by the second week of life and reaching adult levels by the fourth-fifth week. The IL-2-deficient production was the result of both T-cell immaturity (or low numbers) as well as macrophage-accessory cell deficiency. In summary, the inefficiency of CTL generation early during the postnatal development is complex and cannot be attributed to deficiencies of a single component. The present studies, however, cannot explain the reason for the earlier appearance of alloreactivity in ontogeny.