Conparing Insulin Dependent Diabetes Mellitus and AIDS

DBRINLEY dbrinley at
Mon Jan 22 07:21:49 EST 1996

      Introduction: This Article attempts to explain why most children
born to women who are HIV positive do not develop AIDS. At the end of the
article I also include a simple, relatively inexpensive procedure for
verifying my conclusions.

      In many ways Insulin Dependent Diabetes Mellitus(IDDM) can be
thought of as the polar opposite of AIDS. First, IDDM is thought to be
caused by an overactive immune system, while many efforts to treat AIDS
have involved trying to stimulate the immune system. Second, CD4+ T cells
are involved in the development of IDDM, while it is generally accepted
that CD4+ depletion is a marker for AIDS. Third, consumption of infant
formula based on cow's milk at or before age 4 months is considered a
causative factor for IDDM, while there is evidence that infant formula
based on cow's milk reduces the presence of HIV, the causative factor for
AIDS until age 4 Months. And finally, there is overwhelming evidence that
most cases of IDDM are caused by milk consumption, while the only person
ever to be cleared of HIV infection was an infant whose only source of
sustenance was formula based on cow's milk.

      Milk protein has been demonstrateed to be capable of enhancing
humoral immunity in the rat model, which is probably why milk consumption
is associated with IDDM. Since milk protein is capable of enhancing
humoral immunity this leaves ony the question as to whether milk
consumption is capable of clearing HIV from an infected individual. I
believe that it can, at least in the early stages of infection, and I hope
to show the mechanism that causes the clearing of the virus.

      When the body is exposed to soluble milk protein the protein is
digested by B and CD4+ lymphocytes. The antigen specific CD4+ T cells
produce interleukin-2(IL-2) and IL-4 which promote the proliferation and
differentiation of B cells. IL-2 is generally associated with the growth
of both B and T lymphocytes, however, IL-4 has been shown to be an
important costimulator for the maturation, production and differentiation
of B cells. In addition IL-4 has been shown to increase the level of Ia
expression and antigen-presenting capacity of B cells. In short, the IL-2
and IL-4 produced as a result of drinking milk will increase the amount of
B cells available to digest antigens and also increase the effectiveness
of those B cells to digest those antigens.

      IL-2 and IL-4, which increase B cell response, also are capable of
increasing the level of CD4+ and CD8+ T cells in the body. IL-2 is
generally associated with growth of T cells, and IL-4 has been shown to be
an important costimulator of resting CD8+ T cells and is the autocrine
costimulator for antigen specific CD4+ T cells. Of special importance for
an infant's developing immune systemis the fact that IL-4 also speeds the
maturation of developing thymocytes.Thymocytes are at least as responsive
to IL-4 as B cells, however the stimulatory activity of IL-4 appears
restricted mainly to the CD4+ and CD8+ population.

      The fact that milk consumption based on infant formula before the
age of 4 months can lead to IDDM can be explained in the following way.
The immature gut of an infant allows a greater amount of antigens access
to the body. The IL-2 and IL-4 generated in response to the antigens in
milk results in a large number of CD4+ T cells to be created. As an infant
begins to develop, his gastrointestinal tract begins to close, allowing
fewer proteins to be exposed to the body. However, the large number of
CD4+ T cells created due to the exposure of the body to milk protein
during the early months of life can set up a chain of events leading to an
increased risk of juvenile diabetes.

      The IL-2 and IL-4 generated in response to the antigens in milk
before age 4 months will also increase the concentration of B cells in an
infant. IL-4 also helps to promote the induction of increased levels of
class II MHC molecules(IA antigens) on resting cells. It has been noted
that long term survivors of HIV typically have a stong cytotoxic T
cell(CTL) response to the AIDS virus, however, it has also been shown that
by the time immunity to a particular strain of HIV develops, viable
mutations already exist. Because of this if an infected person must rely
on CTL response as the only method of controlling HIV, he can never clear
himself of the disease. When B cells bind with antigen, however, point
mutations frequently occur in the V region genes, with mutations favoring
a better antibody fit with antigen selected for expansion and survival. In
this way B cells can be created to match new strains of HIV as they
develop, allowing an infected person to clear themselves of HIV.

      The CD8+ T cells produced as a result of IL-2 and IL-4 also help to
fight HIV infection. It has recently been demonstrated that IL-16, which
is secreted from activated CD8+ T cell suppresses the replication of HIV
and SIV.

      While the effect of soluble milk protein is strongest in infants,
the effect can also be demonstrated in adults. If a healthy adult, who
does not normally drink low fat or skim milk, drinks 8 ounces of low fat
or skim milk per 100 pounds of bodyweight,his CD4+ and B cells will begin
to increase within 2 hours, and the increased levels of lymphocytes will
continue for about 24 hours. While virtually everyone will have increased
levels of lymphocytes as a result of low fat milk consumption, only about
80 percent of the people will experience a significant increase in
lymphocytes.(Low fat milk must be used in adults because of the
differences in their gastrointestinal tracts from those of infants)
Unfortunately, this method for stimulating lymphocye production does not
work for those people who test positive for HIV, probably because CTL in
general and HIV-specific CTL in particular interfere with CD4+ and B cell
production. Indeed, interferon gamma(Ifn-g), which is produced by CTL, is
known to abrogate the stimulatory effect of IL-4, so that depletion of
CD4+ lymphocytes would be expected with long term exposure to CTL.

      Finally, several studies have shown that milk consumption is the
most common stimulus for causing diabetes, while the only person to be
cleared of HIV infection was an perinatally infected infant that was fed
milk based on formula. Of additional interest, however, is a study by Jorg
Schupbach(Journal of Acquired Immune Deficiency Syndrome, Nov, 1994) which
found that all infants born to mothers infected with HIV had IgG
antibodies to HIV-1 at birth. For infants who do not develop detectable
levels of HIV, the prevalence of HIV-reactive IgG declines after birth,
however, there is a transient increase in the presence of IgG reactive
with p24 during months 7-12. This increase in antibodies for gag proteins
could be the result of a marginal increase in the amount of undetectable
HIV present in infants which may occur after an infants gastrointestinal
tract starts to close, and before his immune system develops. Schupbach
also discovered that IgG seropositivity initially declined slowly in
infants that do not develop detectable levels of HIV, followed by more
rapid declines in later months. this pattern of decline in IgG prevalence
is not the normal decay pattern that one would expect if infants did not
have HIV present, but rather the initial reduction in IgG seropositivity
would be expected as the infants cleared thier HIV infections, followed by
a more rapid reduction once the infection was gone. 

      Srisakul Kliks of the University of California in San Fransisco has
said that neutralizing antibodies in the mother play an important role in
reducing (HIV) transmission to the newborn. On the one hand, there is no
known mechanism for the neutralizing antibodies of the mother to prevent
HIV infection in her infant unless the infant is exposed to the virus. On
the other hand, because no expectant mother has cleared HIV infection,
there is no reason to believe that her antibodies would be capable of
clearing her infant of HIV infection. It would be prudent, therefor to
accept the possibility that most, if not all children born to mothers
infected with HIV, that do not develop dectectable levels of HIV, are born
with the infection, but are able to clear themselves of the virus before
it becomes detectable.

      While it would be difficult to prove that all infants born to
mothers infected with HIV are infected with the virus, it can be inferred
in the following way. Three groups of infants are needed: 
          Group 1: Children who are HIV negative according to CDC/ASTPHLD 
                       guidelines, whose mothers are HIV positive.
          Group 2: Children who are HIV negative, whose mothers are HIV
          Group 3: Children with HIV-Specific CTL.

      Assuming that none of these children drink low fat or skim milk,
simply have each of them drink an equal amount of low fat or skim milk per
bodyweight.(Actually, whole milk increase lymphocytes in preteens, but
then it would be necessary to find children who do not drink milk.) Group
1 will show a slightly larger average increase in CD4+ and B lymphocyte
levels than will group 2 because group 3 is removed. And group 3 will show
almost no change in corresponding lymphocytes because CTL produce Ifn-g
and possibly other cytokines which limit CD4+ and B cell proliferation.   

Send questions and comments to Dennis S. Brinley Sr. at DBRINLEY at 

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