RECONSTITUTION OF SCID MICE WITH HEMATOPOIETIC PRECURSORS - A DETAILED ANALYSIS OF GAMMA-DELTA T-CELL RECONSTITUTION

A well-known characteristic of gamma delta T cells is that they are pr oduced in waves during ontogeny, with cells expressing T-cell receptor V gamma 5 appearing early in fetal thymic ontogeny, followed by V gam ma 6, then by other gamma delta T-cell types. In addition, evidence ex ists to suggest that the potential of haemopoietic precursors to gener ate different types of gamma delta T cells changes in ontogeny. We hav e used these observations as the basis for an extensive study of the p otential for haemopoietic precursors isolated from fetal liver, neonat al spleen and adult bone marrow to reconstitute severe combined immuno deficient (SCID) mice. Mice that were reconstituted as newborns with f etal liver cells most closely resembled normal C.B-17 mice with respec t to both lymphocyte numbers and subsets, while mice reconstituted wit h adult bone marrow had fewer cells than normal mice. This deficit spa nned both T and B cells in all organs examined. Among the gamma delta T-cell subsets examined, the ability to reconstitute V gamma 4(+) cell s was particularly dependent on the ontogenic age of the reconstitutin g presursors, with fetal liver cells having the greatest capacity to g enerate V gamma 4(+) cells, and adult bone marrow cells the least. The vast majority of the T cells produced in the reconstituted mice were of donor origin, and the level of reconstitution was found to be depen dent upon some factor other than the presursor frequency.