Role of Class-II Major Histocompatibility Complex
(MHC)-Antigen-Positive Donor Leukocytes in Transfusion-Induced
Alloimmunization to Donor Class-I MHC Antigens
K.J. Kao and
M.L.U. del Rosario
From the Departments of Pathology, Immunology and Laboratory
Medicine, and Pediatrics, College of Medicine, University of Florida,
Gainesville, FL.
It has been shown that peripheral-blood mononuclear leukocytes (MNL)
are responsible for transfusion-induced alloimmunization to donor major
histocompatability complex (MHC) antigens. However, it is not known
which subset of MNL is responsible for this immune response. Because
elimination of class-II MHC antigen-positive passenger leukocytes
effectively prolongs the survival of allografts, it has been
hypothesized that class-II positive MNL are responsible for immunizing
transfusion recipients to donor MHC antigens. To test this hypothesis,
two different approaches were used. First, we compared the
alloantigenicity of BALB/c mice (H-2d) peripheral blood MNL
before and after depletion of class-II positive cells. CBA mice
(H-2k) were used as transfusion recipients. Antibody
development to donor class-I H-2 antigens was determined by flow
cytometry and enzyme-linked immunoassay. After four weekly transfusions
of MNL depleted for class-II positive cells, only 25% of recipient
mice developed antibodies to donor H-2d antigens. In
contrast, all mice transfused with control MNL became immunized.
Second, we studied the alloantigenicity of peripheral MNL from C57BL/6
mice (H-2b) with homozygous deficiency of class-II MHC
molecules in H-2 disparate recipient mice. After transfusions with
class-II MHC molecule-deficient MNL, 0% of BALB/c, 40% of C57BR, and
25% of CBA-recipient mice developed antibodies to donor
H-2b antigen. All control recipient mice were immunized.
The antibody activities of the controls were also higher than those in
the treatment group who became immunized. Thus, our study shows that class-II MHC antigen-positive MNL play a significant role in
transfusion-induced alloimmunization to donor class-I MHC antigens. The
results also support the hypothesis that direct antigen presentation by
donor class-II positive MNL to the immune system of transfusion
recipients is critical for the initiation of humoral immune response to
donor MHC antigens.
Blood, Vol. 92 No. 2 (July 15), 1998:
pp. 690-694
© 1998 by the American Society of Hematology.
