Modulation of F1 cytotoxic potentials by GvHR. Host- and donor-derived cytotoxic lymphocytes arise in the unirradiated F1 host spleens under the condition of GvHR-associated immunosuppression

Abstract

As an approach to dissect complex cellular events that lead to GvHR-associated immune disorders, we followed cytotoxic activities, including NK cytotoxicity, in the spleens of unirradiated F1 hosts undergoing GvHR induced by parental spleen cells. Spleen cells of (B10 X DBA/2)F1 or (B10 X AKR/J)F1 hosts undergoing GvHR induced by parental B10 spleen cells displayed a prompt and marked increase in NK cell activity within 36 hr, and the heightened activity lasted until day 8. The activity then declined abruptly and disappeared on day 12 of GvHR. Inversely, donor B10-derived CTL specifically directed to the opposite parental alloantigens of the F1 hosts emerged in these F1 host spleens on day 8, and the CTL activity reached a peak on day 12 when the host NK cell activity disappeared. During the period that the donor-derived anti-host CTL were present, these F1 host spleen cells lost not only NK cell activity but also the ability to mount in vitro CTL responses. In contrast, the respective F1 strain mice undergoing GvHR induced by the parental DBA/2 or AKR/J spleen cells showed only transient but marked increases in NK cell activity during the initial 36 hr, and then the activity decreased gradually to return to the normal level on day 10. In such GvHR F1 host spleens, donor-derived CTL could never be detected, and the spleen cells showed normal in vitro CTL responsiveness during the entire observation period of 16 days. These results are discussed from the viewpoint of genetically defined cellular events that lead to the GvHR-associated immune disorders.