Characterization of RT6-Bearing Rat Lymphocytes. II. Developmental Relationships of RT6(-) and RT6(+)T Cells

The derivation of RT6(+) T cells from postthymic RT6(-) T cells in weanling rats was formally demonstrated by the intravenous transfer (“parking”) of highly purified populations of RT6(-) lymph node T cells into thymectomized, irradiated, and bone-marrow-reconstituted (TXBM) RT6(+) and RT7 alloantigen-disparate recipients. Parallel experiments in irradiated and bonemarrow- reconstituted rats, and in rats whose RT6(+) T cells had been depleted by injection of DS4.23 anti-RT6.1 mAb, suggested that the transit time between the pre-RT6(+) and the RT6(+) T-cell compartments approximated 4-5 days. A more precise estimate of the transit time was made by linear regression analysis of the generation of RT6(+) T cells in rats that were treated with DS4.23 mAb at timed intervals after thymectomy. This study indicated that 50% of the pre-RT6 T cells differentiated into RT6(+) cells within 4 days, 75% within 8 days, and more than 90% within 16 days. Despite the apparent absence of pre-RT6(-) T cells 3 weeks after thymectomy, numerous RT6(-) T cells persisted for at least 10 weeks in thymectomized rats, even after treatment with DS4.23 mAb. Moreover, these RT6(+) T cells failed to generate RT6(+) T cells after transfer into adoptive hosts. Quantitative and phenotypic analyses indicated that this population of “true” RT6(-) T cells: (1) constitutes approximately 50% of the total RT6(-) T cells normally found in control rats; (2) contains CD4 and CD8 subsets; (3) expresses both the CD5 pan-T-cell antigen (which is absent from NK cells) and the R73 α/β TCR constant-region determinant; and (4) lacks sIgM. Hence, the present results indicate that the “true” RT6(-) and the RT6(+) T-cell subsets have stable antigenic phenotypes and represent developmentally discrete populations of postthymic cells in normal rats. This is supported by associated phenotypic and functional studies that suggest that the “true” RT6(-)T-cell subset contains antigenically naive and/or autoreactive clonotypes, whereas the RT6(+) T-cell subset contains memory and/or regulatory cells. It remains to be determined whether the “true” RT6(-) and the RT6(+) subsets represent separate lineages of T cells or a single lineage at different stages of activation or maturation.