CD8+ effector cells responding to residual class I antigens, with help from CD4+ cells stimulated indirectly, cause rejection of "major histocompatibility complex-deficient" skin grafts.
BACKGROUND
Skin grafts from mice that are deficient in the expression of both class I and class II major histocompatibility complex (MHC) antigens are rejected rapidly by normal recipients.


METHODS
To determine the mechanism of this rejection, MHC-deficient skin grafts were placed on recipients with different degrees of antigenic disparity and on recipients depleted of selected T cell subpopulations. In addition, the recipient's T cells were examined in vitro for their responses before and after graft rejection.


RESULTS
The results indicate that (1) CD4+ cells provide help for this rejection by recognizing donor antigens presented by recipient class II antigens, and (2) CD8+ cells can participate as effector cells, recognizing residual class I antigens expressed by the MHC-deficient grafts.


CONCLUSIONS
The primary conclusion from these studies is that the supposedly MHC-deficient mice actually do have sufficient class I antigen expression to cause skin graft rejection. This finding prevents the use of these mice to answer definitively the question of whether grafts entirely lacking MHC antigens would be rejected. However, these studies do illustrate two important (although previously recognized) features of allogeneic skin graft rejection: (1) that rejection can be initiated by help provided entirely through the indirect pathway, and (2) that help provided through the indirect pathway is available for effector T cells sensitized directly by donor cells. However, the results from these and other studies suggest that indirect effector mechanisms would probably be able to destroy truly MHC-deficient grafts under some circumstances.
Lee
R S
RS
Tranplantation Unit, General Surgical Services, Harvard Medical School, Massachusetts General Hospital, Boston 02114, USA.
Grusby
M J
MJ
Laufer
T M
TM
Colvin
R
R
Glimcher
L H
LH
Auchincloss
H
H
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000502:physiology*; D008285:Major Histocompatibility Complex / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D016038:Skin Transplantation / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology; D050378:T-Lymphocytes, Regulatory / Q000502:physiology
D015395:Histocompatibility Antigens Class I