Sera from AIDS patients inhibit the responsiveness of normal lymphocytes in allogeneic and autologous mixed lymphocyte cultures.

We analyzed the effects of 10 sera from patients with AIDS on the responsiveness of normal lymphocytes in allogeneic and autologous mixed lymphocyte cultures (MLR and AMLR). Results show that all AIDS sera significantly inhibit lymphocyte responsiveness in either MLR or AMLR of non-T/T and T/T type. Experiments performed to asses the effects of heat inactivated sera or sera fractions (obtained by ultracentrifugation on membranes with predetermined pore diameters) on either stimulator or responder cells, showed that the suppressive effects are attributable to heat stable factors with a wide range of molecular weights that act mainly on responder T cells. Present data suggest that circulating factors with inhibitory effects on MLR and AMLR responses can be found in AIDS sera. These factors might contribute to the immunosuppression of AIDS patients.

Major histocompatibility gene products and human immunodeficiency virus infection.

In the present paper we analyze the role of major histocompatibility gene products, the human leukocyte antigens, in the pathophysiology of the acquired immunodeficiency syndrome. No association has been found between human leukocyte antigen (HLA) frequencies and human immunodeficiency virus type 1 (HIV 1) infection, whereas significant associations have been reported in some populations between some HLA haplotypes and the appearance of either opportunistic infections or secondary cancers. With regard to the human leukocyte class I antigens, their role as restriction elements in presenting HIV 1 to virus-specific cytotoxic T lymphocytes seems to be established. An increase in the serum levels of their soluble forms that correlate with disease stage has also been demonstrated. These circulating molecules could interfere with the immune response to HIV 1 and could contribute to the development of the immunodeficiency. Antigenic similarities have been detected between human leukocyte class II antigens and HIV 1 envelope proteins. These homologies could explain both the presence in some HIV-positive sera of anti-HLA class II antibodies that mediate the lysis of CD4(+)-HLA class II+ T cells and the false-positive reaction of some HIV-negative sera, which contain anti-HLA class II antibodies, in tests for HIV 1 antibodies. Reduced levels of some complement factors (the human leukocyte class III antigens) have been detected in HIV-infected subjects. These defects could play a role in the progression of the disease and affect both the clearance of HIV 1 and complement-mediated antibody responses. The data reported in this review suggest that HLA antigens may be involved in several steps of the immune deficiency of HIV-infected subjects and thus contribute to the pathophysiology of acquired immunodeficiency syndrome.

Simple ELISA method for the evaluation of soluble HLA class I antigens in human serum.

A simple sandwich ELISA method has been developed for the quantification of soluble HLA class I antigens (s-HLA) in human serum. The assay utilizes the monoclonal antibody Q6/64, directed to a monomorphic determinant of the HLA alpha-chain, to capture the antigen and the biotinylated NAMB1 monoclonal antibody, directed to beta 2-microglobulin, as the detection antibody. The extract of the LG-2 lymphoid cell line and pooled sera from 100 healthy subjects are utilized as standards. The arbitrary value of 100 s-HLA Relative Units/mL (RU/mL) is given to the 1:20 dilution of pooled human sera whose optical density value corresponds to the one of the extract of 1 x 10(6) LG-2 cells (6.25 micrograms/mL protein concentration). The assay is easy to perform, specific, reproducible (intra- and inter-assay variations ranging from 3.2% to 8.87%), sensitive (detection limit of 6 RU/mL), and needs a small amount of serum (0.1 mL). The mean serum levels of s-HLA found in 100 healthy normal subjects are 41.9 +/- 13.4 RU/mL. The potential uses of the method are discussed.

HLA class I soluble antigen serum levels in HIV-positive subjects--correlation with cellular and serological parameters.

HLA Class I soluble antigen serum levels have been evaluated in 178 subjects who were positive for human immunodeficiency virus (HIV) and in 66 HIV-negative controls. The serum levels of HIV p24 antigen, interleukin 2 receptor (IL 2r), CD8 soluble antigen (CD 8ag), B2-microglobulin (B2-m), and neopterin (Npt), as well as the number of CD4+ and CD8+ T cells were also evaluated. Results show that mean HLA class I serum levels of HIV-positive subjects: (1) are significantly higher than controls (p less than 0.001); (2) increase with disease progression (67.7 RU/ml, 103.4 RU/ml, and 169.6 RU/ml for subjects belonging to groups II, II, and IV of the Centers for Disease Control [CDC] classification, respectively); (3) correlate with HIV p24 antigen, IL2r, and CD 8 soluble antigen levels. Present data show that elevated levels of HLA class I soluble antigens, correlating with disease stage, are found in sera of HIV-positive subjects. Circulating HLA class I molecules, interfering with some immune functions, might contribute to the pathogenesis of the immune deficiency of HIV-positive subjects.