Osteopetrosis in the IA rat cured by spleen cells from a normal littermate

The Clausen modification of the peripheral blood buffy coat leukocyte migration test was used to test patients with multiple sclerosis, normal subjects and patients with other neurologic diseases for cell-mediated immunity to commercial measles virus, purified nuclear core material from a human neurotropic strain of measles virus, as well as to commercial preparations of rubella, mumps and parainfluenza HA2. Leukocytes of multiple sclerosis patients showed significantly less mean inhibition of migration in the presence of both measles antigens, mumps and parainfluenza but no difference from controls when incubated with rubella. No correlation could be found between the degree of migration inhibition and concomitant serum anti-measles neutralization antibody titers to the same strain of virus. The use of purified viral antigens might result in more meaningful studies of the status of cellmediated immunity to viral antigens in multiple sclerosis. The relationship of our findings to other studies in this area and to the pathogenesis of multiple sclerosis is discussed.     

Measles virus-induced migration inhibition of human leukocytes in vitro: an expression of cell-mediated immunity?

Attempts were made to establish measles virus-induced migration inhibition of human leukocytes as an in vitro test of cell-mediated immunity to the virus. Crude material from cell cultures infected with two different strains of measles virus was used as antigen in the capillary modification of the test. Both virus preparations induced migration inhibition. Incubation with puromycin indicated that the inhibition was dependent on protein synthesis, which has been regarded as a characteristic feature of an immunologically specific inhibition. However, no difference was found when the migration inhibition of leukocytes from donors without clinical and serological evidence of previous measles infection was compared with that of leukocytes from donors with such evidence. It is concluded that the migration inhibition induced by crude measles virus material does not necessarily measure cell-mediated immunity to the virus.     

"Vibrio alginolyticus" enteritis

The leukocyte migration inhibition test (L.M.T.) was utilized for in vitro studies of cell mediated immunity in gynecologic malignomas. Autogenous peripheral blood leukocytes from 50 patients with a carcinoma of the cervix uteri were studied in about 100 tests. There was found an inhibition of the migration of the autogenous leukocytes in 25 of 47 tests of patients with a CCI without evidence of metastasis or widespread disease. However, the migration of autogenous leukocytes from patients with metastasis or widespread disease (CCII) were only inhibited in 14 of 46 cases. At normal tissue were inhibited in 15 of 89 cases the migration of the autogenous leukocytes.     

Epidemiologic pathology of gastric ulcer and gastric carcinoma among Japanese in Hawaii

Cell-mediated immunity in rheumatoid arthritis (RA) was assessed by skin testing with six antigens in 107 patients, 94 of whom were age, sex, and race-matched with healthy individuals or patients with diseases unrelated to immunological abnormalities. 20% of RA patients were anergic. Impaired cell-mediated immunity in the RA patients was manifested by a decrease in the magnitude of skin reactivity as well as a decrease in the incidence of positive reactions to multiple antigens. Depression in cell-mediated immunity was related to age but not to sex, duration of disease, or disease activity. A slight correlation was found between absolute peripheral lymphocyte counts and the number of positive skin tests, and was confirmed by finding an association between lymphocyte counts and the size of skin reactions. A correlation was also found between lymphocyte counts and disease activity. Four explanations of the observed depression in cell-mediated immunity in RA were considered: (1) a preoccupation of the immune mechanism of the host with cell-mediated immunity reactions related to the pathogenesis of the disease; (2) a depression of cell-mediated immune reactivity by a virus infection; (3) depression of cell-mediated immunity by therapy; and (4) immune complex suppression of cell-mediated immunity. No effect of gold therapy was found. The near universal use of salicylates or other anti-inflammatory drugs did not permit investigation of the effect of these drugs on cell-mediated immunity.     

Cell-mediated immunity to Vibrio cholerae with ribonucleic acid-protein fractions of V. cholerae L-form lysates

Different L-form lysate vaccines of Vibrio cholerae serotypes Ogawa and Inaba and their combination along with ethyl alcohol-precipitated ribonucleic acid (E-RNA) and phenol-extracted RNA (P-RNA) fractions of V. cholerae Ogawa lysates were tested for production of cell-mediated immunity. Both E-RNA and P-RNA fractions induced an increase in leukocyte migration inhibition, macrophage migration inhibition, and macrophage aggregation. They also induced delayed hypersensitivity in rabbits. More consistent results were obtained with the P-RNA fraction.     

Absolute diet therapy and antibiotic tolerance in bronchial asthma patients

In 10 patients with bronchial asthma (BA) treated conventionally (control group), 10 BA patients on absolute diet therapy (group 1) and 10 BA patients in absolute diet therapy combined with wheat herb juice (group 2) tolerance to 12 antibiotics of different classes and some immunity factors were determined using a complex of diagnostic methods. The latter implies: case history, humoral and cell immunity defense system tests and special tests (chemical erythrograms and leukocyte migration inhibition test in plane capillary tubes with tested drugs). The data obtained evidence for increased tolerance of the antibiotics in groups 1 and 2 as well as for changes in humoral defense system, especially in immunoglobulin E. The drug tolerance may be a therapeutic criterion of absolute diet therapy in bronchial asthma patients.     

Serum ribonuclease in patients with lung carcinoma

Fifty-one previously untreated cases of lung carcinoma and 7 normal healthy controls were evaluated with respect to serum ribonuclease (S-RNase) levels. Cellular immunity was tested in 22 of these 51 cases by leukocyte migration inhibition test (MIT) using extract of culture cell line of lung carcinoma. S-RNase levels in lung carcinomas were significantly elevated. There appeared to be no difference in S-RNase levels by histological classification. More striking was high S-RNase level in disseminated versus localized cases. MIT results indicated impairment of cellular immunity in those cases of more elevated S-RNase. S-RNase may be implicated in blocking phenomenon associated with neoplastic disease.     

Cell-mediated immunity and blocking factor in ovarian carcinoma

Lymphocyte-mediated cytotoxicity (cell-mediated immunity) to ovarian carcinoma cells and serum blocking factor were measured in 37 patients. Short-term cultures of tumor cells and a low ratio of effector to target cells were used throughout the study, minimizing nonspecific cytotoxicity. Sixteen patients were followed for long periods of time, and correlation with the course of the disease and with therapy could be obtained. Although the level of cell-mediated immunity did not always correspond to the clinical status of the patient, the presence of blocking factor was associated with clinical relapse in 14 of 16 patients. Chemotherapy with single alkylating agents or combinations of drugs caused no significant or permanent depression of cell-mediated immunity as measured in this way. In addition, blocking factor disappeared in 2 patients during remission. It appears that the chemotherapy for ovarian carcinoma may not be significantly immunosuppressive against established levels of cell-mediated immunity and may in certain instances have effects potentially beneficial to the host as evaluated by lymphocyte-mediated cytotoxicity and blocking factor studies.     

In vitro studies during long-term oral administration of specific transfer factor

153 patients suffering from recurrent pathologies, i.e. viral infections (keratitis, keratouveitis, genital and labial herpes) uveitis, cystitis, and candidiasis were treated with in vitro produced transfer factor (TF) specific for HSV-1/2, CMV and Candida albicans. The cell-mediated immunity of seropositive patients to HSV-1/2 and/or CMV viruses was assessed using the leucocyte migration inhibition test (LMT) and lymphocyte stimulation test (LST) in presence of the corresponding antigens, and the frequency of positive tests before, during and after TF administration was studied. The data were stratified per type of test, antigen and the recipients' pathology, and statistically evaluated. For the LMT, a total of 960 tests were carried out for each antigen dilution, 3 different antigen dilutions were used per test. 240/960 tests (25.4%) were found positive during non-treatment or treatment with unspecific TF, whereas 147/346 tests (42.5%) were found positive when the antigen corresponding to the specificity of the TF administered to the patient was used (P < 0.001). When the data were stratified following pathology, a significant increased incidence of positive tests during specific treatment was also observed (0.0001 < P < 0.05). In the LST (1174 tests), a significant increase of thymidine uptake was observed in the absence of antigen (control cultures), during treatment with both specific and unspecific TF, but also in the presence of antigen and/or autologous serum during specific TF administration (P < 0.0001). TF administration also significantly increased the soluble HLA class I antigens level in 40 patients studied to this effect.     

Cell-mediated and humoral immunity in bulls infected with IBR/IPV virus (BHV 1)

Time-related changes in specific cell-mediated immunity (CMI) and in humoral immunity were monitored in 20 bulls, aging 12 to 16 months, in four groups, each consisting of 5 animals. Group I was experimentally and group III-naturally infected with BHV 1 virus, groups II and IV serving as control animals. Tests for CMI included delayed type hypersensitivity (DTH), leukocyte migration inhibitory factor (LMIF) and granulocyte migration inhibitor factor (GMIF-LIF-buffy coat leukocyte migration inhibitory factor) in the presence of BHV I antigen while humoral immunity was tested by serum induced neutralization of the virus (SN) and by estimation of serum IgG, IgG1, IgG2, IgM and IgA levels. Immunologic, virologic and clinical studies were performed two days before infection and 17 timed within 91 days after the infection in bulls of group I and II and 7 times within 42 days after developing the disease in bulls of groups III and IV. The results showed that positive CMI reactions appeared 3 to 4 weeks earlier than positive antibody titers in SN test. The antibodies belonged most probably to IgG1 and IgG2 subclasses.     

Cell-mediated immune response in equine babesiosis

An intradermal skin test, to demonstrate a delayed cutaneous hypersensitivity reaction in Babesia equi infection in donkeys, was developed. A skin reaction to B. equi antigen was elicited in vaccinnated, infected and carrier intact and splenectomised donkeys. The histopathological examination of the skin biopsy revealed infiltration of mononuclear cells and accumulation of oedematous fluid in the deeper layers of the dermis. A leucocyte migration inhibition test was developed and its specificity as an in vitro measure of cell-mediated immunity to B. equi antigen was established. The results of this study demonstrated a correlation between cell-mediated immunity and protection.     

Urethral calculus extraction using a penile ring block anesthetic

Levamisole is known to enhance an impaired immune response. Its function as an immunostimulant was assessed in malnourished children. A total of 26 children suffering from severe protein-calorie malnutrition were selected for the study. Serum immunoglobulins were estimated in these subjects and to assess cell-mediated immunity, enumeration of T lymphocytes and the lymphocyte proliferative response were carried out. The results show an increase in the cell-mediated immunity response in the levamisole-treated group, thereby suggesting that levamisole may help to speed the recovery of malnourished children suffering from various infections.     

The effect of levamisole on cellular immunity in multiple sclerosis

The lymphocyte stimulation test has been standardized in a normal human population using four virus cell-associated antigens (VCAA): human embryonic lung cells infected with the LEC and Norrby strains of measles virus, mumps virus, and vaccinia virus. Following 1 week of treatment with the immunopotentiating drug levamisole, a group of multiple sclerosis (MS) patients was found to have increased lymphocyte stimulation responses toward VCAA and increased delayed hypersensitivity responses towards a battery of skin test antigens. No change in the percentage of short- or long-incubation E rosettes occurred. Measles haemagglutinin inhibition (HI) antibody titres measured before and after the entire course of levamisole therapy (12 weeks) did not change. The neurological status of five out of seven MS patients deteriorated while they were taking levamisole.     

Antiviral and interferon-inducing activity of a new glutarimide antibiotic, 9-methylstreptimidone

Leucocyte migration inhibition by autologous breast tumour cell fractions was mediated by a soluble factor synthesized and released by mononuclear leucocytes and active against migrating granulocytes. This mechanism is similar to that previously described in respect to cell-mediated sensitivity to microbial antigens. Alternative mechanisms involving directly reactive granulocytes or cytophilic antibodies were rarely operative in the migration tests.     

Immunological reactions in pathogenesis of posttraumatic uveitis and eyeball subatrophy

Clinical and morphological examinations of 30 eyes enucleated for relapses of traumatic uveitis and subatrophy caused by grave penetrating wounds involving a complete loss of visual function were carried out and 12 patients were tested for sensitization to tissue antigens by the leukocyte migration inhibition test. Morphological examination revealed cellular reaction in eye membranes, indicating an autoimmune process developing in response to release of the antigenic tissue substances of the eye into the bloodflow and reactive flow of immunocompetent cells towards ocular tissues because of injury to the blood-eye barrier. Detection of sensitization to tissue antigen in the patients confirms this viewpoint. The authors compare the revealed inflammatory process in the injured eye with the graft rejection reaction and find them similar.     

Studies on Pasteurella multocida. III. In vitro assay for cell-mediated immunity

Peripheral blood lymphocytes (PBL) from turkeys immunized against fowl cholera with a bacterin or a live avirulent vaccine (strain CS-148) were cultured in vitro with various antigenic preparations from Pasteurella multocida (strain P-1059). The degree of lymphocyte stimulation (blastogenesis) was quantitated by measurement of the uptake of (3H) thymidine. Higher stimulation indices were obtained with immune lymphocytes rather than nonimmune lymphocytes. Stimulation was specific since PBL from turkeys immunized against P. multocida failed to react with Escherichia coli or Mycoplasma synoviae antigens. These differences were statistically significant as analyzed with the student's t-test. The lymphocyte transformation assay was emphasized as a convenient and useful in vitro indicator of cell-mediated immunity that should help define the role of cell-mediated immunity in P. multocida infections of turkeys.     

Young people in transition: the relationship between homesickness and self-disclosure

To assess cell-mediated immunity to Toxoplasma gondii, we evaluated the expression of the activation antigens CD69, CD71, and CD25 on T lymphocytes by flow cytometry after specific in vitro stimulation of whole blood from 127 T. gondii-positive and 63 T. gondii-negative patients. T lymphocytes from many seropositive individuals did not express CD69 at 24 h after T. gondii antigen stimulation, but CD71 and CD25 were easily detectable on T cells from seropositive individuals 7 days after specific activation. CD25 was mainly expressed by stimulated CD4(+) T cells, and its detection on total T cells was both a sensitive (98%) and a specific (97%) indicator of prior T. gondii infection. These results make flow cytometric detection of CD25 an excellent candidate for screening cell-mediated immunity to T. gondii in vitro and an interesting tool for the diagnosis of congenital infection.     

Hypothalamic self-stimulation and operant activity in the mottled mutant mouse

Cell-mediated immunity to bacterial antigens was studied by intradermal testing, and to contact antigens (cosmetics, environmental chemicals and topical medicaments) by patch testing in 270 children with atopic dermatitis. The incidence of delayed-type immune cutaneous reactions in these patients was lower than in the controls. Contact allergy is a rare finding in the first 4 years of life but its incidence increases subsequently. In subjects with atopic dermatitis the incidence of sensitization by contact with allergens contained in topical medicaments proved to be lower than in subjects with eczema of other types. The data collected points to a reduced cell-mediated immune reactivity in a proportion of subjects with atopic dermatitis.     

Efficacy of transfer factor in treating patients with recurrent ocular herpes infections

Recurrent ocular herpes is an insoluble problem for the clinician. As cellular immunity plays an important role in controlling herpes relapses, and other studies have shown the efficacy of HSV-specific transfer factor (TF) for the treatment of herpes patients, an open clinical trial was undertaken in 134 patients (71 keratitis, 29 kerato-uveitis, 34 uveitis) suffering from recurrent ocular herpetic infections. The mean duration of the treatment was 358 days, and the entire follow-up period 189,121 before, and 64,062 days after TF treatment. The cell-mediated immune response to the viral antigens, evaluated by the lymphocyte stimulation test (LST) and the leucocyte migration test (LMT) (P < 0.001), was significantly increased by the TF treatment. The total number of relapses was decreased significantly during/after TF treatment, dropping from 832 before, to 89 after treatment, whereas the cumulative relapse index (RI) dropped, during the same period, from 13.2 to 4.17 (P < 0.0001). No side effects were observed. It is concluded that patients with relapsing ocular herpes can benefit from treatment with HSV-specific TF.     

Histocompatibility leukocyte antigen-A2-restricted and tumor-specific cytotoxic T lymphocytes from tumor-infiltrating lymphocytes of patient with testicular embryonal cancer

T lymphocytes play an important role in tumor rejection. To understand T cell-mediated specific immunity at the tumor site of testicular embryonal cancer, we investigated whether interleukin-2 (IL-2)-activated tumor-infiltrating lymphocytes (TIL) of a patient with testicular embryonal cancer show histocompatibility leukocyte antigen (HLA)-class I-restricted and tumor-specific cytotoxicity. We established a CD3+CD4-CD8+ cytotoxic T lymphocyte (CTL) line from the IL-2-activated TIL of a 37-year-old patient with testicular embryonal cancer. A 6 h 51Cr-release assay was performed to measure the cytotoxicity of the CTL. The CD3+CD4-CD8+ CTL line showed cytotoxicity against HLA-A2+ tumor cells, including freshly isolated autologous tumor cells, adenocarcinoma cell lines from various organs (lung, breast, pancreas, colon and kidney) and squamous cell carcinomas (esophagus and oral cavity). No other cell lines examined, including an autologous tumor cell line and HLA-A2- tumor cell lines, were lysed by this CTL line. These results suggest the existence of HLA-A2-restricted and tumor-specific CTL at the tumor site of testicular embryonal cancer.