THE POSSIBLE ROLES OF SPERM AND SPERM ANTIBODIES IN THE
PATHOGENESIS AND TREATMENT OF AIDS
Joseph Eldor, MD
Theoretical Medicine Institute,
P.O.Box 12142, Jerusalem 91120, Israel
Intravenous injections of donor sperm may possibly be of
value to AIDS patients. The immunological basis for this
proposal is reviewed in detail. Donor sperm introduced into
the blood of a healthy patient produces anti-sperm
antibodies which may become attached to the T-cells and
cause their depletion. Reintroduction of donor sperm into
the blood of an AIDS patient may reverse the pathogenesis by
the donor sperm combining with anti-sperm antibodies so
allowing the T-cells to recover. HIV is just the common
among the occupational viral infections of AIDS patients. A
clinical trial is proposed.
Primary AIDS infection
The heterogenous clinical manifestations of primary AIDS
infection reflect an immunological response. Subjects
typically present with an illness of acute onset
characterized by fever, lethargy, malaise, myalgias,
headaches, retro-orbital pain, photophobia, sore throat,
lymphadenopathy and maculopapular rash. Meningoencephalitis
may also occur. Lymphadenopathy occurs in approximately 70%
of people with primary AIDS infection (1). An erythematous
maculopapular rash is common during primary HIV infection.
The rash generally resolves within 1 week. Immunohistology
reveals a predominantly CD4+ cell infiltrate around the
superficial dermal vessels in the presence of a normal
epidermal layer. These cells might present p24 antigen to
CD4+ lymphocytes, eliciting a delayed-type hypersensitivity
reaction (2). The lymphopenia that occurs during the first 2
weeks of primary AIDS infection (3) affects both the CD4+
and cd8+ subsets, and the level of CD4+ cells can be as low
as that seen in people with AIDS (4). The interval between
infection and development of AIDS has been estimated to have
a median duration of approximately 10 years (5). Changes in
the immune system mark the period before AIDS, as measured
by laboratory markers as well as by clinical findings and
One of the major obstacles to understanding the pathology of
HIV infection in humans is that we do not know precisely how
the presence of the HIV genome in only a minority of CD4+
T-cells leads to the gradual destruction of the immune
system. CD4 has two identified roles on T-cells: it acts
like an adhesion molecule in the class II-target cell
interaction (7), and it has been proposed to have a signal
transduction capacity in a transient complex with the T-cell
receptor (8). The immune system of individuals infected with
HIV is affected by loss of CD4+ cells (9) and by loss of
T-helper-cell function (10). The loss of T-helper cell
function is independent of the decline in CD4+ cell counts.
The loss of such function precedes a significant reduction
in CD4+ cells counts (11).
Soluble CD4 proteins can bind to HIV and HIV-infected cells
and release gp120 from free virus and virus-infected cells
(12). Recombinant CD4-IgG fusion protein can prevent HIV
infection in chimpanzees (13). Duesberg (14) claimed that
AIDS virus is just the most common among the occupational
viral infections of AIDS patients and those at risk for
AIDS, rather than the cause of AIDS. Other viral infections
of AIDS patients and those at risk for AIDS include
Epstein-Barr and cytomegalovirus in 80-90% (15), and herpes
virus in 75-100% (14). In addition, hepatitis B virus is
found in 90% of drug addicts positive for antibody to AIDS
virus (16). Gottlieb et al. (17), who described the first 4
patients with AIDS in the literature, commented that they
"acknowledge the possibility that cytomegalovirus infection
was a result rather than a cause of the T-cell defect, and
that some other exposure to an undetected micro-organism,
drug, or toxin made these patients susceptible to infection
with opportunistic organisms, including cytomegalovirus".
Bisset (18) suggested a possible role for mycoplasma as a
"superantigen cofactor" to the ongoing process of HIV
Sperm cells with AIDS
Erlander (19) proposed that sperm cells which apparently are
also capable of complexing with HLA-DR and CD4 receptors,
could, under certain circumstances, such as a joint
interaction of HIV and sperm with the same T-cells, induce
immune reactions to HIV. Anti-sperm antibodies (an allogenic
immunization) occurred in 19 out of 26 homosexual sperm
recipients (2). Similar evidence for alloimmunization was
found also in the female of a heterosexual couple who
routinely practiced anal intercourse (20).
Hypogonadism is present in many male patients with AIDS (21)
and testicular atrophy has been reported as an autopsy
finding (22). El-Demiry and James (23) examined
immunocytochemically specimens of human testis, epididymis,
vas deferens, prostate and seminal vesicles. They found that
T-lymphocytes are the predominant immunological cell type in
all these tissues. Of particular interest was the
preponderance of suppressor-cytotoxic T-cells within the
epithelium and lamina propria of those tissues where the
blood-testis barrier is weak or deficient. They suggested
that these macrophages may provide an ancillary back-up
protection against the risk of escaped sperm antigens
following alterations in the integrity of the blood-testis
Haas et al. (24) showed that washing sperm even 18 times
does not reduce the sperm antibody level. Using media with
high level of serum appear to cause a drop in the sperm
antibodies. However, the sperm antibodies are only masked
and reappear when the spermatozoa are resuspended in
serum-free media (25).
Spermatozoa injected into the bloodstream tend to accumulate
in the capillaries, eventually to be taken up by the
reticuloendothelial system (26).
Spermatozoa are known to be sequestered within the
seminiferous tubules by a blood-testis barrier formed by
tight junctions between Sertoli cells and thus prevented
from being exposed to the immune system. Alternatively, it
is likely that active immuno-suppression exists within the
testes (27). Spermatozoa can penetrate somatic cells and
fuse with their nuclei (28). Such nuclear fusion, other than
in normal fertilization, can give rise to malignant
transformation (29). Stein-Werblowsky (30) suggested that
allogenic ectopic spermatozoa having gained access via anal
fissures or lacerations of the rectal mucosa may survive in
the vascular (portal) system and therein impinge on
endothelial cells, eventually invading them and fusing with
their nuclei. This may result in an endothelioma, i.e.
There is a high frequency of antibodies to seminal plasma in
Kaposi`s sarcoma patients (31). Antibodies to spermatozoa
and to circulating immune complexes are present in
apparently healthy homosexuals (32). Human seminal fluid
also contains components that potentially can suppress the
immune response (33). Weekly deposition of pooled rabbit
semen into the rectum in healthy male rabbits resulted in
the appearance of immune complexes and antibodies to sperm
and to peripheral lymphocyte antigens (34).
Intravenous injections of donor sperm to AIDS patients
The concept that blood transfusion might not be deleterious
to graft outcome was proposed in the late 1960s (35). Many
people did not at first accept the finding that blood
transfusion actually improved renal allograft survival (36).
In 1973, Opelz et al. (36) reported that the outcome of
renal allografts in patients who were never blood transfused
before transplantation was worse than that of recipients who
had been transfused. Blood transfusion has been demonstrated
to induce antibodies against the T-cell alloantigen-specific
receptors, i.e. anti-idiotypic antibodies (37).
The preparation of an antiserum against lymphoid cells was
first described by Metchnikoff in 1899 (38). Antilymphocyte
globulin was first used clinically in 1966 (39).
Antilymphocyte globulin was used in vitro to remove
T-lymphocytes from the bone marrow graft (40).
Antilymphocyte globulin is prepared by injecting horses,
rabbits, pigs, or goats with human lymphoid cells in the
form of buffy coat, thoracic duct lymphocytes, thymus or
lymphoblastoid cell lines and the polyclonal antiserum which
results contains a variety of antibodies, some of which have
organ-specificity, some all-specificity and some
Circulating immune complexes are capable of reacting with Fc
or complement receptors on T- and B-lymphocytes and
macrophages and thus modulate both cellular and humoral
immunity. Direct deposition of circulating immune complexes
in kidneys or arteries may lead, respectively, to
glomerulonephritis (41) or atherosclerosis (42). Spermatozoa
and T-lymphocyte share common surface antigens (43). An
immune response to spermatozoa may therefore lead to the
production of antibodies that interfere with
T-lymphocyte-mediated functions. A major mechanism of HIV
entry into cells is by binding of the HIV envelope gp120 to
the cell CD4 receptor (44). Soluble CD4 acts by binding HIV
extracellularly, thereby preventing entry of HIV into CD4+
cells (45). There is a 5-10-fold greater frequency of
HIV-infected cells in the primary lymphoid tissues than in
the blood (46).
Intravenous injections of donor sperm are suggested to be
given to AIDS patients. It is proposed that the donor sperm
introduced into the blood of an AIDS patient will attach to
the anti-sperm antibodies existing there and attacking the
T-cells. The donor sperm will also take off those antibodies
from the T-cells, so allow the T-cells to recover. An
immunological basis for the cause and cure of AIDS is
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