The present study was undertaken to define the cellular mechanisms involved in the rejection of major histocompatibility complex (MHC) class I disparate skin grafts by mice depleted of CD8+ T cells in vivo. Mice were effectively depleted of CD8+ T cells by adult thymectomy followed by in vivo administration of anti-CD8 monoclonal antibody (mAb) and then engrafted with allogeneic skin. We found that CD8 depleted mice did reject MHC class I disparate skin grafts, but only when the grafts also expressed additional alloantigens. Despite the marked depletion of CD8+ T cells in these mice, we found that their rejection of MHC class I disparate grafts was mediated by CD8+ cytolytic T lymphocyte (CTL) effectors that had escaped depletion. These CD8+ CTL effectors were unique in that: (a) their generation was dependent upon the injected anti-CD8 mAb and upon exposure to class I MHC alloantigens expressed on the engrafted skin, and (b) their effector function was resistant to blockade by anti-CD8 mAb. We observed that the additional alloantigens coexpressed on MHC class I disparate grafts that triggered graft rejection in CD8-depleted mice could be MHC-linked or not and that they functioned in these rejection responses to activate third party specific CD4+ T helper (Th) cells to provide helper signals for the generation of CD8+ anti-CD8 resistant CTL effector cells. Thus, mice depleted of CD8+ T cells by thymectomy and in vivo administration of anti-CD8 mAb harbor a unique population of anti-CD8 resistant, CD8+ effector cells that mediate anti-MHC class I responses in vivo and in vitro, but require help from third party specific Th cells to do so.
Skip Nav Destination
Article navigation
1 June 1991
Article|
June 01 1991
Cellular basis of skin allograft rejection across a class I major histocompatibility barrier in mice depleted of CD8+ T cells in vivo.
A S Rosenberg,
A S Rosenberg
Cytokine Biology Division, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892.
Search for other works by this author on:
T I Munitz,
T I Munitz
Cytokine Biology Division, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892.
Search for other works by this author on:
T G Maniero,
T G Maniero
Cytokine Biology Division, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892.
Search for other works by this author on:
A Singer
A Singer
Cytokine Biology Division, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892.
Search for other works by this author on:
A S Rosenberg
Cytokine Biology Division, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892.
T I Munitz
Cytokine Biology Division, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892.
T G Maniero
Cytokine Biology Division, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892.
A Singer
Cytokine Biology Division, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1991) 173 (6): 1463–1471.
Citation
A S Rosenberg, T I Munitz, T G Maniero, A Singer; Cellular basis of skin allograft rejection across a class I major histocompatibility barrier in mice depleted of CD8+ T cells in vivo.. J Exp Med 1 June 1991; 173 (6): 1463–1471. doi: https://doi.org/10.1084/jem.173.6.1463
Download citation file:
Sign in
Don't already have an account? Register
Client Account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Sign in via your Institution
Sign in via your InstitutionEmail alerts
Advertisement