Billie J. Wilson

Vasectomy: immunologic effects in rhesus monkeys and men.

In order to determine: 1) if antibodies against spermatozoa are formed in vasectomized males and 2) the long-range physiological effects of vasectomy spermatozoa and serum from 30 vasectomized men and 26 vasectomized rhesus monkeys were tested. The average spermagglutinin titer increased over time in the human samples while decreasing and remaining low in most of the monkey samples. Sperm-immobilizing antibodies were detected in some rhesus monkeys within 2 weeks after vasectomy. Ammonium sulfate precipitation showed spermagglutinating antibody in the immunoglobulin fraction. In rhesus monkeys aggluntination was not the result of secretion from the accessory sex glands since both ejaculated and epididymal spermatozoa agglutinated in the presence of vasectomized monkey serum; hence the antigens recognized by the spermagglutinating antibody must have been present before accessory fluids were added. In investigating the long-range effects of vasectomy monkeys who had been vasectomized for 12 months did not differ from sham-vasectomized animals in white blood counts glucose levels urea nitrogen creatinine total protein globulins acid phosphatase serum glutamic pyruvic transaminase and insulin. Animals vasectomized for 4-8 years showed no significant difference in urea nitrogen creatinine albumin gamma globulin or the A/G ratio when compared with their own earlier blood values or appropriate controls. Urine from these long-vasectomized animals with sperm-agglutinin titers showed no abnormalities. Based on this data vasectomy appears to be a safe method of sterilization that causes no deleterious effects.

Distribution of type D retrovirus sequences in tissues of macaques with simian acquired immune deficiency and retroperitoneal fibromatosis

Horizontally acquired SAIDS retrovirus type 2 (SRV-2), a type D retrovirus related to the Mason-Pfizer monkey virus, has been associated with the simian acquired immunodeficiency syndrome (SAIDS) including retroperitoneal fibromatosis (RF) in several macaque species at two primate research centers. Virus specific gene sequences are present in lymphoid and RF tissues but not in muscle tissue of diseased macaques or in any tissues of uninfected normal monkeys. Serologic and restriction endonuclease mapping techniques have defined unique SRV-2 strains in the Celebes (SRV-2C) and rhesus (SRV-2R) macaques at the Oregon Regional Primate Center, SRV-2 is related to both MPMV and SAIDS type 1 retroviruses and it has no detectable molecular homology with the human AIDS retroviruses.

Cell-mediated immunity in vasectomized rhesus monkeys *

Cell-mediated immunity in rhesus monkeys that had been vasectomized for 2, 4, 7, or 11 years was measured by lymphocyte blastogenesis following stimulation with concanavalin A, phytohemagglutinin (PHA), and pokeweed mitogens. Several of the 7- and 11-year vasectomized animals had significantly reduced PHA reactivity when compared with control animals, and the percentage of animals with reduced PHA reactivity increased with time after vasectomy.

Rhesus Monkey Micro Mixed Lymphocyte and Mitogen Reactivity: Optimal Conditions and Normal Variability*

Optimal conditions for the rhesus monkey micro mixed lymphocyte system with multiple automated harvesting of samples were evaluated. Parameters studied were cell concentration, length of culture period, methods of inactivation of cell populations, supplementation of media, type of culture plates, and changes in the reactivity of cells from individual animals over an extended time period.

Virus-associated deficiencies in the mitogen reactivity in celebes black macaques (Macaca nigra)

Celebes black macaques (Macaca nigra) with a history of diabetes mellitus, recurrent bacterial and protozoal infections, diarrhea, anemia, weight loss, anorexia, and a high mortality were studied to determine their immune status. Two groups of monkeys, healthy and unhealthy, were formed on the basis of a clinical assessment. The proliferative response and the pokeweed-mitogen-induced polyclonal IgG response of peripheral blood mononuclear cells of unhealthy monkeys were significantly less than the responses of healthy monkeys. The percentage of HLA-DR+ cells varied greatly in unhealthy monkeys. The OKT4/OKT8 ratios of unhealthy monkeys were generally greater than the ratios of healthy monkeys. Unhealthy monkeys usually had smaller percentages of OKT8+ cells than did healthy monkeys. The two groups of monkeys were examined for the presence of a syncytial forming retrovirus by a coculture assay involving Raji cells, a human B lymphoblastoid cell line. A type D retrovirus was detected in the unhealthy group but not in the healthy group. Retroperitoneal fibromatosis was detected in several monkeys in the unhealthy group.

Reduced T cell reactivity in vasectomized rhesus monkeys: association with histocompatibility type.

The capacity of peripheral lymphocytes from rhesus monkeys which had been vasectomized for 7 or 11 years to stimulate and respond to normal rhesus lymphocytes in mixed lymphocyte cultures (MLC) was tested to determine whether vasectomy affects immunologic reactivity. The ability to respond in MLC, a T cell function, was significantly reduced in the 11-year vasectomized animals and in two 7-year vasectomized animals. The ability to stimulate in MLC, a B cell function, was significantly increased in the 11-year vasectomized group. MLC reactivity of normal lymphocytes cultured in plasma from vasectomized animals and lymphocytes from vasectomized animals cultured in normal plasma was not altered, ruling out serum effects in the reduction of MLC responsiveness in these vasectomized animals. Seventy-five per cent of the vasectomized animals with markedly reduced MLC reactivity had the RhL-A determinates 19 and 24, indicating an association between the tendency toward reduced MLC reactivity after vasectomy and histocompatibility type.

Transmission of simian acquired immunodeficiency syndrome with a type D retrovirus: immunological aspects

Simian acquired immunodeficiency syndrome (SAIDS) was transmitted to four of four rhesus macaques with blood from rhesus macaques naturally infected with a type D retrovirus, simian retrovirus-2 (SRV-2). Three of the four blood recipients died with SAIDS at 13, 15, and 26 weeks postinoculation. The fourth animal is alive with SAIDS. All four test monkeys became viremic and produced antiviral antibody. None of the inoculated monkeys produced measureable neutralizing antibody to SRV-2. The survivor produced higher levels of antiviral antibody than the monkeys that died. Phytohemagglutinin and concanavalin A reactivity of peripheral blood lymphocytes was depressed from weeks 6 to 12 after inoculation. Clinical findings included development of splenomegaly in all four monkeys, and diarrhea in two monkeys. Blood counts remained within the normal range except for a depression in the number of polymorphonuclear lymphocytes in two monkeys. Hematocrits were decreased in two monkeys just prior to their death. All four test monkeys developed lymph node atrophy and bone marrow hypoplasia. Total proteins and immunoglobulin production were normal. This report provides evidence that SRV-2, as well as other type D retroviruses, causes SAIDS in macaque species.

Neutralizing antibody in Celebes black macaques recovering from infection with simian acquired immunodeficiency syndrome retrovirus type 2

Neutralizing antibodies that block the ability of simian acquired immunodeficiency syndrome (SAIDS) retrovirus type 2 (SRV-2) to induce syncytium formation in cultures of Raji cells have been found in the serum of nonviremic Celebes black macaques (Macaca nigra). Serum from Celebes macaques that are viremic have little or no neutralizing activity. The neutralizing antibodies were shown to block viral infectivity. The group of monkeys with neutralizing antibodies in their serum exhibited a dramatic improvement in their health from 1982 to 1984. The correlation of neutralizing antibodies with clinical improvement suggests that neutralizing antibodies may play a critical role in limiting the pathogenic effects of SAIDS retrovirus infection and in helping eliminate the infection.

Cell transfer studies in immunosuppressed mice: the role of the macrophage.

Summary In cell transfer experiments C3H recipients, which had been immunosuppressed by cycloleucine, were capable of initiating a primary response to sheep erythrocytes if they were given macrophage-antigen mixtures frolm normal or from Cytoxantreated donors. Similarly prepared macrophages from cycloleucine-treated donors and crude cell suspensions derived from normal spleens were ineffective. If the recipients were immunosuppressed with Cytosan, the results were reversed, in that normal spleen cell-antigen mixtures stimulated antibody synthesis but normal macrophage-antigen mixtures did not. The data which were obtained with drug-treated and with Xirradiated recipients support the concept that antigen processing by the macrophage is necessary for initiating a primary type immune response. They also demonstrate the selective susceptibility of macrophages and spleen cells to immunosuppressive drugs.

Tumor specific immunity to mouse melanoma in vitro.

Summary An in vitro assay that measures the ability of mouse spleen cells to inhibit DNA synthesis (IDS) of syngeneic melanoma tumor cells was used in the evaluation of tumor immunity. The IDS assay was used in the measurement of both specific immunity mediated by spleen cells from tumor-bearing mice and nonspecific tumor cell growth inhibition mediated by normal spleen cells. Specific IDS was first demonstrable 2 weeks after injection of 106 B-16 tumor cells sub-cutaneously and persisted during advanced stages of disease. Changes in spleen cell IDS activity were correlated with changing mitogen reactivity during the course of tumor growth. A portion of the spleen cells mediating nonspecific IDS was removed by nylon wool filtration, but the effector cells exhibiting specific immunity were not removed by this procedure. Immune spleen cells did not need to synthesize DNA or divide to inhibit tumor cell DNA synthesis.