Phenotypic abnormalities in CD8+ T lymphocyte subsets in patients with rheumatoid arthritis.

We analyzed the cell surface phenotype of CD8+ cells in both peripheral blood and synovial fluid (SF) of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Utilizing the monoclonal antibodies anti-CD45RA, anti-CD29 and anti-S6F1-, one can define both suppressor effector (CD45RA+CD29-S6F1-) and killer effector (CD45RA-CD29+S6F1+) cells within the CD8 population. In patients with OA, normal proportions of CD8+CD45RA+, CD8+CD29+ and CD8+S6F1+ cells were found in both peripheral blood and SF. The peripheral blood of patients with RA, in contrast, showed a decreased percentage of CD8+CD45RA+ cells (13.4 +/- 2.6) (p less than 0.05), but a normal percentage of CD8+CD29+ and CD8+S6F1+ cells. In the SF of patients with RA, we observed a more dramatic decrease in CD8+CD45RA+ suppressor effector cells (6.4 +/- 5.0) (p less than 0.001), a significant increase in killer effector cells as measured by both CD8 + CD29+ (35.5 +/- 9.9) (p less than 0.001) and CD8 + S6F1+ cells (28.2 +/- 11.4) (p less than 0.01). These changes may contribute to the immunologic abnormalities previously noted in this disease and may provide some insight into the pathophysiologic mechanisms of RA.     

Cardiac output determination during intravenous cardioangiography using x-ray fluorescence analysis

Cardiac output was determined with an indicator dilution technique during digital venous angiography of the left ventricle in 11 patients. The contrast medium injected into the right atrium was used as indicator. During and after the injection of contrast medium one blood sample per second was obtained through a catheter placed in the descending aorta. The samples were analyzed for iodine content with x-ray fluorescence analysis and cardiac output determined ad modum Stewart-Hamilton. Thermodilution was used as a reference method. The results indicate that the indicator dilution method with the use of contrast medium might be used for calibration of videodensitometric methods for blood flow measurements.     

Combination of ABO blood group incompatibility and glucose-6-phosphate dehydrogenase deficiency: effect on hemolysis and neonatal hyperbilirubinemia

The incidence (%) of hyperbilirubinemia (serum bilirubin ≥257 μmol/l) was similar in neonates with a combination of ABO incompatibility and glucose-6-phosphate dehydrogenase (G-6-PD) deficiency (45%), with ABO incompatibility (54%) or G-6-PD deficiency (37%), alone (ns). Carboxyhemoglobin values, corrected for inspired CO, were similarly elevated in all three groups (0.87 ± 0.32%, 0.82 ± 0.29%, 0.76 ± 0.18%, respectively, ns), but correlated with bilirubin only in those with ABO incompatibility alone. ABO-incompatible/G-6-PD-deficient neonates, compared with those with either condition alone, are not at increased risk for hemolysis or hyperbilirubinemia.     

Contrasting effects of cyclophosphamide and prednisolone on the phenotype of human peripheral blood leukocytes

The cell surface phenotype of human peripheral blood mononuclear cells has been characterized before and after intravenous injection of cyclophosphamide or prednisolone. Low doses of cyclophosphamide (100-600 mg/m2) temporarily decrease levels of circulating B lymphocytes. Slightly higher doses of cyclophosphamide (200-600 mg/m2) produce transient depression of T8-, M1-, and Ia-positive cells. After doses of 200-400 mg cyclophosphamide/m2, T4-positive cells are spared, resulting in a transient elevation of the T4/T8 ratio. With higher doses of cyclophosphamide (greater than or equal to 600 mg/m2), all T cells are affected and the T4/T8 ratio declines to pretreatment levels. By contrast, intravenous injection of prednisolone at 40 mg/m2 reduces the T4/T8 ratio. Levels of both T4 and T8 cells decline, but T4 cells are affected more markedly than T8 cells.     

The role of functionally distinct helper T lymphocyte subpopulations in the induction of human B cell differentiation

Human helper T lymphocytes can be dissected into two functionally distinct subpopulations based on expression of the CD45RA (2H4) or CD45R0 (UCHL-1) surface antigens. While both subpopulations are able to induce equivalent levels of B cell activation and proliferation, only the CD4+CD45RA- subpopulation is capable of inducing B cell differentiation in pokeweed mitogen (PWM)-stimulated cultures. To define the mechanism responsible for the dichotomy between induction of proliferation and differentiation by the two CD4+ subpopulations, we examined the abilities of the purified T cell subpopulations to produce lymphokine mRNA following T cell activation. Northern analysis revealed that both subpopulations produced interleukin (IL) 2 and interferon (IFN)-gamma mRNA following PWM activation. The CD4+CD45RA- subpopulation, however, produced higher levels of IFN-gamma mRNA and the CD4+CD45RA+ cells produced higher levels of IL 2 mRNA. Neither subpopulation elaborated detectable mRNA for IL 4, IL 5 or IL 6. Of greatest significance was that the addition of recombinant or T cell-derived lymphokines could not compensate for the inability of the CD4+CD45RA+ subpopulation to induce B cell differentiation in PWM assays. Direct T-B cell contact was required for the optimal induction B cell differentiation in these assays, suggesting that CD4+CD45RA+ T cells were deficient in their ability to directly deliver the T cell-B cell signals required for B cell differentiation. These results suggest that the differential ability of the two subpopulations of CD4+ T cells to induce B cell differentiation does not result from differences in lymphokines elaborated, but may result from differences in their abilities to interact directly with B cells to initiate differentiation.     

A monoclonal antibody that blocks class II histocompatibility-related immune interactions

Previous studies using conventional hetero- or isoantisera have indicated the involvement of class II (Ia) molecules in presentation of soluble by monocytes to inducer T lymphocytes, stimulation of inducer T cells in MLR, and recognition of Ia-bearing targets cells by cytotoxic T lymphocytes (CTL). The experience in using monoclonal anti-Ia reagents capable of blocking these phenomena in the human system is limited. Recently, however, we have characterized a lytic IgG2a monoclonal antibody, 9–49, that binds to functionally significant class II molecules. This antibody blocks (in the absence of complement): (1) specific binding of peripheral blood lymphocytes (PBL) to antigen-pulsed monocyte monolayers, (2) proliferation of PBL in response to soluble antigen (tetanus toxoid or mumps) or cell surface class II antigen stimulation in allogeneic or autologus MLR, (3) proliferation of cloned T4+ (inducer) lymphocyte cell lines to class II antigens, (4) generation of cytotoxic lymphocytes during allogenic MLR, and (5) recognition (and killing) of class II-bearing target cells by T4+ CTL clones. Proliferation and CTL activity of a T8+ clone is unaffected by the 9–49 antibody. These results indicate the usefulness of this monoclonal reagent in studies evaluating the functional role of Ia molecules in immune recognition phenomena.