Differential effects of manipulating signaling in early T cell developmentin intestinal intraepithelial lymphocytes and thymocytes

A pre-TCR-CD3 signal is required for the efficient maturation of CD4(-)CD8( -) thymocytes to the CD4(+)CD8(+) stage. This study addressed whether a sim ilar signal is required for maturation of intestinal intraepithelial lympho cytes (IEL) that may develop extrathymically. We have shown previously that IEL from mice deficient for CD3-associated zeta chains include an immature population of CD3(-)CD8 alpha alpha(+) cells expressing cytoplasmic TCR be ta chains but lacking detectable surface TCR alpha beta, CD16 and B220. Her e we stimulated the appearance of such IEL in epsilon(+/-)zeta(-/-) mice by expression of an activated Lck transgene or in vivo treatment with anti-CD 3 epsilon. Anti-CD3 epsilon treatment of RAG-deficient animals also yielded CD16(-)B220(-) IEL. In contrast, expression of a TCR beta transgene in rag -1(-/-) mice did not stimulate the appearance of CD3(-)CD8 alpha alpha(+)CD 16(-)B220(-) cells. Taken together these data indicate that although anti-C D3 epsilon treatment and Lck(F505) assist in catalyzing a CD16(+)B220(+) -- > CD16(-)B220(-) transition, these manipulations are not equivalent to a pr e-TCR signal in IEL lymphocytes.