Page 1388 - Veterinary Immunology, 10th Edition

on T cells and by suppressing macrophage prostaglandin E 2
VetBooks.ir production. Supplemental vitamin E may enhance immune

function in adult cats and elderly humans.

Cytokines and Monoclonal Antibodies

Allograft rejection intensity can be minimized by reducing T cell
numbers through administration of an antiserum specific for T

lymphocytes produced in rabbits or horses. Thus polyclonal anti-
lymphocytic serum (ALS) suppresses the cell-mediated immune
response and leaves the humoral immune response relatively intact.
In practice, ALS is of variable efficiency and specificity and may

cause severe side effects as a result of global immunosuppression.
ALS-treated mice have been shown to accept rat xenografts,
whereas clinical use of ALS in humans has not been universally
accepted as useful. As a result of these issues with polyclonal

antibodies, much more specific mouse monoclonal antibodies have
been produced. The first to be employed was monoclonal anti-CD3.
Anti-CD3 is directed only against T cells and is effective in
reversing allograft rejection in humans. An even more specific

monoclonal antibody is anti-CD25. This binds to the α chain of the
IL-2 receptor and so prevents lymphocyte activation. Anti-CD25
helps prevent acute renal allograft rejection and, since it does not
cause T cell depletion, has fewer adverse effects and results in fewer

opportunistic infections than crude ALS.
Monoclonal antibodies against canine CD4 and CD8 have been
used to control rejection of canine renal allografts. They are very
effective, even with highly mismatched mongrel dogs. Both anti-

CD4 and anti-CD8 must be used together, and their
immunosuppressive effect lasts for about 10 days. (The dogs
eventually develop neutralizing antibodies against these mouse
antibodies.) These are especially effective in combination with

cyclosporine.
In some diseases, especially those due to excessive immune
function, it may be beneficial to neutralize excessive cytokine
activity using monoclonal antibodies against a cytokine or against
its receptor. Monoclonal antibodies directed against these targets

are widely employed in humans. The original monoclonal

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