Lymphocyte transformation induced by autologous cells. XVI: Distinctive role of discrete regions of class I MHC antigens in the autologous mixed leucocyte reaction.

The role of Class I major histocompatibility complex (MHC) molecules in the autologous (AMLR) and allogeneic mixed lymphocyte reactions was investigated by using monoclonal antibodies (MoAb) directed to polymorphic MHC determinants. The AMLR from subjects with the HLA-A2 phenotype was consistently inhibited by the anti-HLA-A2 MoAb, CR11-351, and the inhibition was dose-dependent and complete even at low antibody concentrations. The allogeneic MLR was inhibited by CR11-351 less than 30% when HLA-A2-bearing cells were used either as stimulator or responder cells. Addition of interleukins 1 and/or 2 to the AMLR in the presence of the inhibiting MoAbs did not restore the proliferative response. These studies suggest that Class I MHC polymorphic determinants, or closely related structures, participate in the induction of the AMLR.

The role of immunity to cartilage proteoglycan in adjuvant arthritis. Intravenous injection of bovine proteoglycan enhances adjuvant arthritis.

It has been suggested that autoimmunity to the proteoglycan (PG) component of cartilage plays a major role in the etiology of adjuvant arthritis (AA), which occurs in rats, but not in mice, after injection of CFA. In order to more directly investigate this role, bovine and human cartilage PG were used to modulate AA, and immunity to PG was assessed. Immunization of rats or mice with PG by itself does not induce arthritis. However, in rats, a single i.v. injection of soluble PG, given 1 wk before injection of CFA, results in a significant increase in incidence and severity of the arthritis induced. Rats injected with CFA have both antibody and delayed type hypersensitivity (DTH) to PG. Upon pretreatment of rats with PG i.v., both DTH and antibody titers to PG are increased. Rats immunized with PG in IFA have high titers of anti-PG and strong DTH to PG, which are also enhanced by pretreatment with PG i.v., although none of these animals develops arthritis. In contrast to these findings in rats, when mice are pretreated with PG i.v., DTH to PG induced by injection of CFA is lower, whereas anti-PG titers are higher than in unpretreated controls. The results presented here show that, in rats, i.v. injection of PG synergizes with CFA in the induction of AA, and enhances both humoral and cellular immunity to PG. The findings support the hypothesis that immunity to PG is of importance in AA, although under the conditions of these experiments immunity induced by PG alone is clearly not sufficient for the induction of arthritis.

Long-term growth of human T cell lines and clones on anti-CD3 antibody-treated tissue culture plates.

Long-term growth of antigen-specific human T cells requires, in addition to IL-2, periodic exposure to antigen and accessory cells. In certain cases, accessory cells are not available or their presence in culture is undesired. We have developed a method of growing and sustaining human T cell lines and clones in long-term tissue culture in the absence of specific antigen or accessory cells. The requirement for antigen and/or accessory cells could be replaced by a monoclonal antibody to the CD3 determinant of human T cells (OKT3) bound to the surface of plastic tissue culture wells. Autoreactive, alloreactive, and antigen-reactive T cell lines and clones were maintained in culture for 8-12 weeks without antigen or accessory cells. The antigen specificity of these T cells was maintained.

Lymphocyte transformation induced by autologous cells: XVIII. Impaired autologous mixed lymphocyte reaction in subjects with AIDS-related complex.

T cells from patients with AIDS-related-complex (ARC) and normal controls were studied for their proliferative response in the autologous mixed lymphocyte reaction (AMLR). Cells from ARC subjects failed to proliferate in autologous MLR compared to normal controls. This defect was not attributable to an altered ratio of T4 to T8 cells, as purified T4 cells from ARC subjects also failed to proliferate in autologous mixed lymphocyte culture. In contrast, T cells from ARC subjects proliferated normally in response to allogeneic non-T cells, and non-T cells from ARC patients stimulated allogeneic T cells as well as did non-T cells from normal controls. Furthermore, there was no significant alteration in the 2H4 (suppressor-inducer) or 4B4 (helper-inducer) subsets of the T4 cell population in these patients. We conclude that an early immunologic defect that accompanies HTLV-III infection is a loss of the T cell response to autologous non-T cells.

Autoimmunity to articular collagen in patients with osteoarticular syndromes.

We studied the occurrence of autoimmunity to articular antigens in 39 patients with noninflammatory osteoarticular syndromes and 60 controls. Cell mediated immunity (CMI) was measured by assaying for leukocyte inhibitory factor (LIF) in supernates of mononuclear leukocytes cultured with native human collagen (types I, II, or III) or proteoglycan monomer. After stimulation with type II collagen, but not other antigens, 27/39 patients and 13/60 controls had positive LIF assays (p less than 0.001). In controls, but not in patients, CMI was associated with positivity for the HLA antigen DR4. No patient had antibodies to native type II collagen. These findings may reflect normal responses to articular injury or suggest that CMI contributes to the pathogenesis of osteoarticular syndromes. But they also emphasize that peripheral blood reactivity is not a certain reflection of synovial immunopathology.

Preparation of deuterium-labeled cocaine and benzoylecgonine.

The preparation of deuterium-labeled cocaine and benzoylecgonine by a site-specific method is reported. This method involves the reductive dehalogenation of appropriately substituted derivatives by a NaBD4 - PdCl2 system. By the judicious choice of halogen-substituted aromatic systems, a wide variety of specifically deuterated compounds of biological interest can be prepared.