The pattern of clonal deletion of putative I-E-reactive (Vβ11) and Mls-reactive (Vβ3) T cells was evaluated and compared by cytofluorographic and immunohistochemical methods in a model of neonatal H-2 tolerance and in I-E- or Mls-bearing strains of mice which normally delete these cell populations (self-tolerance). The ontogeny of deletion of Vβ11+ cells was studied by evaluating thymic changes from birth until maturity in B10.S (H-2s/I-E-), B10.A (H-2k/d/I-E+) and B10.S mice intravenously infused at birth with (B10.S×B10.A) F1 lymphohaematopoietic cells. The reduction in Vβ11+ cells was most prevalent in the medullary region of the naive B10.A and neonatally injected B10.S animals and was corroborated by flow cytometry which demonstrated a marked reduction in single CD4 and CD8 positive Vβ11 T cells when compared to naive B10.S mice. However, immunohistochemistry illustrated that 'deletion' was never complete since Vβ11+ cells remained in the thymic cortex and splenic lymphoid follicles. By comparison, DBA/2 mice (Mlsc+ and previously documented to have decreased levels of Vβ3+ cells) showed a different pattern of deletion of Vβ3+ T cells than what was found for T cells bearing Vβ11 in animals deleting this population. DBA/2 thymi contained fewer thymic Vβ3+ cells and there was more complete elimination of these cells, particularly in the periphery, by flow cytometry and immunohistology. The mice which do not delete Vβ3 cells (Mlsc-) showed that the majority of Vβ3+ cells were located in the medulla with a few cells distributed in the cortical region. This pattern was notably different than the distribution of Vβ11 cells in thymi. Despite their location by histology, the majority of remaining Vβ3+ cells were dual CD4/CD8 positive (CD4+CD8+) by flow cytometric analysis. Our data illustrate that Vβ11 and Vβ3 T cells appear to be eliminated (i.e. 'deleted') at similar stages of maturation (single positive) during self-tolerance as well as in a neonatal H-2 tolerance model. However, the degree of elimination and the location of the cells remaining in these mice is dramatically different, depending on which T cell population is being evaluated and which deleting ligand is presented intrathymically. Thus, the accepted tenet of dual CD4+CD8+ cells localizing to the thymic cortex appears to have exceptions. Moreover, the variable efficacy with which T cells are eliminated in the thymus may be an important determinant that influences a host's capacity to manifest long-term tolerance to a particular alloantigen.
ASJC Scopus subject areas
- Immunology and Allergy