Since organ transplantation was introduced over a quarter of a century
ago, it has become a widespread remedy for life-threatening disease.
Several thousand kidney transplants are performed each year in the
United States alone. In addition, physicians have succeeded in transplanting
the heart, lungs, liver and pancreas.
The
success of a transplant-whether it is accepted or rejected-depends
on the stubbornness of the immune system. For a transplant to "take,"
the body of the recipient must be made to suppress its natural tendency
to get rid of foreign tissue.
Scientists
have tackled this problem in two ways. The first is to make sure
that the tissue of the donor and the recipient are as similar as
possible. Tissue typing,
or histocompatibility
testing, involves matching the markers of self on body tissues;
because the typing is usually done on white blood cells, or leukocytes,
the markers are referred to as human
leukocyte antigens (HLA). Each cell has a double set of six
major antigens, designated HLA-A, B, C, and three types of HLA-D-DR,
DP, and DQ. (HLA-A, B, and C are the same as the class I antigens
encoded by the genes of the major histocompatibility complex; HLA-D
region molecules are the class II MHC antigens.)
Each
of the HLA antigens exist-in different individuals-in as many as
20 varieties, so that the number of possible HLA types reaches about
10,000. Histocompatibility testing relies on antibodies to determine
if a potential organ donor and recipient share two or more HLA antigens,
and thus are likely to make a good "match." The best matches are
identical twins; next best are close relatives, especially brothers
and sisters.
The
second approach to taming rejection is to lull the recipient's immune
system. This can be achieved through a variety of powerful immunosuppressive
drugs. Steroids suppress lymphocyte function; the drug cyclosporine
holds down the production of the lymphokine interleukin-2, which
is necessary for T cell growth. When such measures fail, the graft
may yet be saved with a new treatment: OKT3 is a monoclonal antibody
that seeks out the T3 marker carried on all mature T cells. By either
destroying T cells or incapacitating them, OKT3 can bring an acute
rejection crisis to a halt.
Not
surprisingly, any such all-out assault on the immune system leaves
a transplant recipient susceptible to both opportunistic infections
and lymphomas. Although such patients need careful medical followup,
many of them are able to lead active and essentially normal lives.