CD4-CD8-C.B-17 SCID thymocytes enter the CD4+CD8+ stage in the presence of neonatally grafted T cells

The aim of this work was to study the selection of donor T cells and their influence on thymic development in C.B-17 scid/scid (severe combined immunodeficient; SCID) mice during chronic graft-versus-host disease (GVHD). Recipient SCID mice (H-2d), neonatally grafted with allogeneic peripheral T cells from CBA/J strain (H-2k) of mice, only developed a mild acute GVHD, and were, at the chronic stage, devoid of pathological 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+CD8+ (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 possessed the highest frequencies of endogenous DP cells (25-95%). In contrast to previous findings, peripheral donor T cells from allogeneic and syngeneic mice, infiltrating the host thymus, had a positive effect on the development of endogenous DP thymocytes. Furthermore, these thymocytes were developmentally blocked at the DP stage, occasionally in combination with the expression of CD25, CD44 and CD117 but in the absence of T-cell receptor (TCR) expression. Also, at this time-point, the CBA/J donor TCR Vbeta repertoire was equal to that of normal CBA/J mice, but purified responding donor cells were proliferatively inhibited against H-2d stimulators in ex vivo mixed lymphocyte cultures. In contrast, the same responders showed a pronounced proliferation against syngeneic H-2Kk stimulators, suggesting either a reversion from anergy of autoreactive CBA/J T cells or a vast expansion of multiple self-reactive T-cell clones, when parked in a milieu with a lower concentration of self-antigens.