Elevated levels of antibodies to cow's milk proteins, i.e., beta-lacto
globulin (BLG) and bovine serum albumin (BSA), have been associated wi
th IDDM. We observed enhanced cellular immune response by a proliferat
ion test of peripheral blood mononuclear cells to BLG in 22 of 40 (55%
) patients with newly diagnosed IDDM compared with 7 of 32 healthy chi
ldren (22%) (P = 0.004, chi(2) test). The median stimulation index to
BLG was 3.3 in patients and 1.5 in healthy children (P = 0.003, Mann-W
hitney U test). No difference was found in cellular reactivity to othe
r cow's milk proteins, such as BSA or alpha-casein, or to a dietary im
munogenic protein, ovalbumin. Cellular responsiveness to BLG was not a
ssociated with HLA-DQB1 risk alleles of IDDM, which suggests that imm
une response to the protein does not only reflect the accumulation of
these HLA alleles in the patients with IDDM. We suggest that enhanced
cellular immune response to dietary BLG may reflect a disturbance in t
he regulation of immune response to oral antigens in IDDM. This kind o
f defect may play a fundamental role in the development of beta-cen au
toimmunity in IDDM.