CD4(-) CD8(-) C.B-17 SCID THYMOCYTES ENTER THE CD4(-CELLS() CD8(+) STAGE IN THE PRESENCE OF NEONATALLY GRAFTED T)

The aim of this work was to study the selection of donor T cells and t heir influence on thymic development in C.B-17 scid/scid (severe combi ned immunodeficient; SCID) mice during chronic graft-versus-host disea se (GVHD). Recipient SCID mice (H-2(d)), neonatally grafted with allog eneic peripheral T cells from CBA/J strain (H-2(k)) of mice, only deve loped a mild acute GVHD, and were, at the chronic stage, devoid of pat hological symptoms. Thymic cell numbers of injected mice differed from 10(5) to 1.2 x 10(7) at 2-3 weeks post-injection (p.i.), and from 4 x 10(5) to 8.5 x 10(7) at 2 months p.i. In these mice, the thymus size was correlated to the CD4(-) CD8(-) (double negative; DN) to CD4(+) CD 8(+) (double positive; DP) cell ratio, where at 2 months p.i, 8 out of 16 treated SCID mice contained 5 x 10(6) cells or more and also posse ssed the highest frequencies of endogenous DP cells (25-95%). In contr ast to previous findings, peripheral donor T cells from allogeneic and syngeneic mice, infiltrating the host thymus, had a positive effect o n the development of endogenous DP thymocytes. Furthermore, these thym ocytes were developmentally blocked at the DP stage, occasionally in c ombination with the expression of CD25, CD44 and CD117 but in the abse nce of T-cell receptor (TCR) expression. Also, at this time-point, the CBA/J donor TCR VP repertoire was equal to that of normal CBA/J mice, but purified responding donor cells were proliferatively inhibited ag ainst H-2(d) stimulators in ex vivo mixed lymphocyte cultures. In cont rast, the same responders showed a pronounced proliferation against sy ngeneic H-2K(k) stimulators, suggesting either a reversion from anergy of autoreactive CBA/J T cells or a vast expansion of multiple self-re active T-cell clones, when parked in a milieu with a lower concentrati on of self-antigens.