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BACKGROUND The authors established the genotype frequencies of cytochrome P450 (CYP1A1/MspI, CYP2E1/PstI, and CYP2E1/DraI), glutathione-S-transferase (GSTM1 and GSTT1), and p53 (exon 4/AccII and intron 3/16-base pair duplication) gene polymorphisms in cervical carcinoma patients and controls and evaluated the association between the specific genotype or genotype combinations of these polymorphisms and the risk of cervical carcinoma. METHODS In this case–control study, the genotypes of 181 human papillomavirus (HPV)-16 or HPV-18 positive cervical carcinoma patients and 1–to-1 age-matched controls were determined using a polymerase chain reaction-based technique. RESULTS Among these polymorphisms, the individuals carrying arginine/proline genotypes of p53 showed a 9.5-fold increase of cervical carcinoma risk (95% confidence interval [CI], 4.9–18.6) compared with those individuals carrying arginine/arginine genotypes. The frequency of overall GSTT1 null genotypes also was significantly higher in cervical carcinoma patients compared with that of GSTT1 positive genotypes (P = 0.003; odds ratio [OR] = 1.9; 95% CI, 1.2–2.9). The genotype combination of p53 and GST played a more important role in describing the relative risk of cervical carcinoma. The individuals carrying both the arginine/proline genotype of p53 and the null genotype of GSTT1 showed a 3.5-fold increase of cervical carcinoma risk (95% CI, 1.8–7.1) compared with those individuals carrying both the arginine/arginine genotype of p53 and the GSTT1 positive genotype. In the patients who were stratified into the two age groups, the null genotypes of GSTT1 (69.1% vs. 45.5%; P = 0.016) and GSTM1 (61.8% vs. 40.0%; P = 0.028) in cervical carcinoma were significantly overrepresented in the younger age subgroup (age 40 years or younger) compared with those of controls. Especially in this age group, the individuals carrying both null genotypes of GSTT1 and GSTM1 showed a 17.8-fold increase of cervical carcinoma risk (95% CI, 2.2–141.0) compared with the individuals carrying both positive genotypes of GSTT1 and GSTM1. CONCLUSIONS The results of the current study suggested that the arginine/proline genotype of p53, independently or in conjunction with the GSTT1 null genotype, could affect the genetic susceptibility for cervical carcinoma, and HPV positive women carrying both null genotypes of GSTT1 and GSTM1 have an increased risk of cervical carcinoma developing before age 40 years. Cancer 2000;88:2082–91. © 2000 American Cancer Society.

We previously reported the generation and characterization of a panel of CD4(+) autoreactive T cell clones that suppress development of autoimmune diabetes in non-obese diabetic (NOD) mice. We showed that the protective capacity of the T cell clones correlated with secretion of an activity that potently inhibits allogeneic mixed lymphocyte reaction (allo-MLR). In this report, we describe the biological characteristics of the allo-MLR inhibitory activity (MLR-IA, short for mixed lymphocyte reaction inhibitory activity) secreted by the protective T cell clone, NOD-5. MLR-IA has little effect on initiation of proliferation in an allo-MLR, but it potently inhibits the maintenance and amplification of the proliferative response. MLR-IA is also capable of inhibiting concanavalin A (Con A) stimulated splenic responder T cell proliferation. MLR-IA is reversible in vitro and is not restricted by MHC class I or II proteins. MLR-IA does not affect IL-2 receptor expression of responding T cells and has no effect on IL-2-dependent proliferation of CTLL-20 T cells. Partially purified MLR-IA inhibits IL-2 production in a primary allo-MLR, and decreases IFN-gamma production during secondary allo-MLR and Con A activation, whereas it enhances IL-4 production in both primary and secondary Con A activation. MLR-IA is not neutralized by combination of antibodies specific for transforming growth factor-beta, IL-10, tumor necrosis factor-alpha/beta or IFN-gamma, suggestive of a novel activity. MLR-IA is ammonium sulfate precipitable, sensitive to protease digestion and is destroyed by boiling, indicating that a protein moiety is part of its active structure. Our work suggests that a potentially novel immunoregulatory activity, capable of inhibiting T lymphocyte proliferation and IFN-gamma production, and stimulating IL-4 production, may regulate development of autoimmune diabetes in NOD mice.