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PubMed1975

Comparative in vitro sensitivity of twom methylcholanthrene-induced murine sarcoma lines to humoral and cellular immune cytotoxicity.

MC57M and G are the tissue-culture derivatives of two methylcholanthrene-induced murine C57Bl sarcomas. Their sensitivity to immune cytoxic3, cytostatic or cytolytic spleen cells and sera was compared in parallel in vitro assays. The level of cross-reactivity displayed by the two lines was found to depend on the nature of the immune effector rather than on the assay which was used. It was high with immune spleen lymphocytes, alone or in the presence of decomplemented antisera, and low with antisera in the presence of rabbit complement. MC57G cells were more sensitive than MC57M cells to both effectors. Both cell lines were insensitive to antibody-dependent cell-mediated cytotoxicity. Preliminary evidence is presented, suggesting a probable involvement of embryonic and Moloney leukemia virus-induced cell surface antigens in the vitro sensitization of the two tumor lines to immune sera.

Animals↗
PubMed1994

Cellular immune response to human renal-cell carcinomas: definition of a common antigen recognized by HLA-A2-restricted cytotoxic T-lymphocyte (CTL) clones.

Cytotoxic T lymphocyte (CTL) clones directed against autologous renal-cell carcinoma (RCC) cell lines were generated by mixed lymphocyte/tumor-cell culture (MLTC) using peripheral blood lymphocytes (PBL). A CD8+, CD4- CTL clone MZ1257-CTL 5/30 with high cytolytic activity for the autologous tumor cell line MZ1257-RCC was established. No lysis of the autologous EBV-transformed B lymphocytes (EBV-B) or K562 cells was observed. A panel of HLA-A2-matched allogeneic RCC lines was recognized by CTL 5/30. Further specificity analysis showed a cross-reactivity with HLA-A2-matched allogeneic tumor cells of various origins, especially melanoma. CTL 5/30 was also cross-reactive with several HLA-A2-positive allogeneic normal kidney cells in culture. The restriction element identified for CTL 5/30 was HLA-A2, as shown by blocking of cytotoxicity using an anti-HLA-A2 monoclonal antibody (MAb) and by resistance of an HLA-A2-negative melanoma variant SK29-MEL. 1.22 against lysis by CTL 5/30. In this report we demonstrate HLA-A2-restricted recognition of a T-cell-defined antigen on autologous renal-cancer cells. This antigen is also expressed and recognized in association with HLA-A2 on normal kidney cells in culture and other HLA-A2-positive tumor cells. It may therefore be a normal differentiation antigen to which tolerance is incomplete in the renal-cell cancer system investigated.

Antibodies, Monoclonal↗
PubMed1984

Apheresis donor safety--changes in humoral and cellular immunity.

Modern techniques of mechanical hemapheresis have made it possible to selectively remove vast quantities of lymphocytes and plasma immunoglobulins, and the concentration of these substances in donor blood can fall below the normal range. It is feared that this may lead to immunosuppression; a condition associated in some clinical settings with infections, malignancy and autoimmune diseases. Using primary immunodeficiency diseases and induced immunodeficiency states (for example, therapeutic lymphocytapheresis, chronic thoracic duct drainage and intestinal lymphangiectasia) as models to judge competency of the immune system, it can be predicted that body defense mechanisms can become defective when serum IgG levels are less than 200 mg/dl or the blood lymphocyte count is less than 1000/microliter. However, impaired immunologic function can occur in the presence of normal quantities of these substances in the blood stream; conditions that may be related either to imbalances of immune regulatory factors or to qualitative (rather than quantitative) abnormalities of the immune system. A number of investigators have documented the losses of lymphocytes and plasma immunoglobulins incurred by donors experiencing mechanical hemapheresis. In addition, both the immediate and long-term decreases in the concentration of these substances in donor blood have been reported. In summary, the immediate decreases in blood lymphocyte counts and serum immunoglobulin concentrations are of slight to moderate degree and are without known adverse effects. Less information is available regarding long-term alterations of the immune system, and little data have been collected from prospective studies in which large numbers of donors have been thoroughly evaluated by modern techniques. In general, results of many laboratory studies have been altered. However, these abnormalities have been transient for the most part, and it has been difficult to document clinically significant adverse effects. Thus, the quantities of blood lymphocytes and plasma immunoglobulins that can be removed from healthy donors without causing significant immediate or long-term harm is unknown. Bearing these limitations in mind, the following recommendations are suggested regarding the frequency of repeated mechanical plasma-and-cytapheresis. 1) The usual requirements for whole blood donation must be met if the frequency of mechanical hemapheresis does not exceed once every eight weeks.(ABSTRACT TRUNCATED AT 400 WORDS)

Blood Donors↗
PubMed1979

The absence of differences in cellular immunity in elderly individuals with and without delayed local cutaneous reactions to influenza vaccine.

Two groups of elderly subjects who received bivalent influenza virus vaccine were identified. Those in Group I manifested marked local reactions, suggestive of delayed hypersensitivity reactions, whereas those in Group II, matched with Group I for vaccine preparation, had no cutaneous reactions. In vitro assays of immune function were performed on pairs of subjects from the two groups and included serum immunoglobulin and complement levels, antibody response to vaccine, lymphocyte transformation to mitogens (phytohemagglutinin, pokeweed mitogen and concanavalin A) and antigens (streptokinase-streptodornase, influenza virus vaccine antigens and multiple mixed lymphocytes), and polymorphonuclear leukocyte chemotactic responsiveness. There was no demonstrable correlation between delayed local cutaneous reaction and preservation of in vitro cell-mediated immune function in these elderly individuals.

Age Factors↗
PubMed1984

Cellular immune response to infection with respiratory syncytial virus and influence of breast-feeding on the response.

Virus-specific lymphocyte transformation (LTF) activity in vitro was examined in 78 infants with various forms of illness due to respiratory syncytial virus (RSV) infection. In 73 subjects with lower respiratory tract disease, significant LTF activity was often detected within one week after onset of initial symptoms, and responses characteristic for each clinical form were observed in the subsequent rise. Thus, mean activity in subjects with tracheobronchitis increased gradually, with the maximum response being detected at the fourth week after the onset of illness. In subjects with pneumonia the response was rather low during the first week of illness, and then a sharp increase of activity was observed at the second week. Although patients with bronchiolitis elicited similar levels of the activity until the first week, the response was significantly suppressed during the subsequent two weeks. The response at the second week in this group was significantly lower than those of corresponding specimens obtained from patients with pneumonia (p less than 0.01) or tracheobronchitis (p less than 0.05), suggesting a close association of the responsiveness with underlying mechanisms of bronchiolitis induced by RSV. The present study further indicated a possibility that breast-feeding of RSV-infected infants may alter levels of the LTF activity in these subjects.

Adult↗
PubMed1985

Cellular immune responses in mice challenged with an amyocarditic variant of Coxsackievirus B3.

An amyocarditic variant of a temperature-sensitive (ts) mutant derived from the parent myocarditic variant Coxsackievirus B3 (CVB3m) was studied in a murine model of CVB3m-induced myocarditis to assess virus-induced antigens and their possible role in the disease process. Amyocarditic variant ts5R induced a heart tissue antigen(s), extractable by hypertonic KC1, which inhibited migration of peritoneal exudate cells from CVB3-inoculated myocarditic mice in an agarose droplet cell-migration-inhibition assay. The ts5R variant was amyocarditic at inoculum doses of 10(3) to 10(8) plaque-forming units per mouse, but in cyclophosphamide-immunosuppressed mice, ts5R induced myocarditis. Viable ts5R served as a vaccine and protected mice against CVB3m-induced myocarditis. Murine neonatal skin fibroblasts (MNSF) infected with either virus served as in vitro targets and were lysed by splenic cytotoxic T lymphocytes from mice inoculated with either virus variant. ts5R and CVB3m replicated to similar titers in murine neonatal skin fibroblasts (MNSF) at 24 hr postinoculation (pi), but differences in titers were found by 72 hr pi. Levels of natural killer cell activities in spleens of ts5R-inoculated mice were slightly lower than in spleens of CVB3m-inoculated mice at 7 days pi. The data suggest that viral induction of new antigens on target cells and viral induction of specific cytotoxic T lymphocytes that recognize these antigenic changes do not always result in induction of myocarditis.

Animals↗
PubMed1988

Humoral and cellular immunity to papillomavirus in patients with cervical dysplasia.

The cell-mediated and humoral immune responses to human papillomavirus (HPV) were tested in groups of patients with various degrees of cervical intraepithelial neoplasia (CIN) using a lymphocyte proliferation assay (LPA) as a measure of circulating sensitised T-cells and an enzyme-linked immunosorbent assay (ELISA) for antibodies. Twenty-three of 92 patients (25%) gave stimulation indices (S.I.) greater than two to at least one of the several antigen preparations tested in the LPA. Of 282 patients, 144 (50.1%) showed ELISA indices (E.I.) greater than one to HPV-1 and/or HPV-2 antigens prepared by disruption of purified virions. No correlation was found between positive responses in either test and the presence in cervical biopsies of koilocytes (considered pathognomonic for HPV infections), or between positive responses and the degree of dysplasia observed. Rather, positive antibody and T-cell responses corresponded with a history of past or present skin warts. Although antibody was detected in 42/86 (48.8%) women who thought they had never had warts, only 2/24 (8.3%) with no known history gave a positive S.I. in LPA.

Antibodies, Viral↗
PubMed2006

Time course characteristics of human herpesvirus 6 specific cellular immune response and natural killer cell activity in patients with exanthema subitum.

The time-course of cell-mediated immunity in exanthema subitum is not well documented. The lymphoproliferative response to purified human herpesvirus 6 (HHV-6) antigen and to phytohemagglutinin was measured and natural killer (NK) cell activities determined in three consecutive specimens obtained biweekly from 18 young children and infants with exanthema subitum. Virus isolation and PCR detection of virus DNA and determination of neutralization antibody to HHV-6 and -7 were also carried out. The magnitude of the HHV-6 specific lymphoproliferative response varied; however, in most cases the time course kinetics revealed a low response in the acute phase with a subsequent gradual increase. In contrast, NK cell activities were high in the acute phase and declined gradually during convalescence. The lymphoproliferative response to phytohemagglutinin did not show a consistent trend in kinetics of time; however, dynamic changes in activity were observed in patients during the acute and convalescent periods. The results suggest that NK cells play a major role in resolving acute phase infection while specific lymphocyte activity develops later. The cause of the delayed development of HHV-6 specific lymphoproliferative response is unknown. The lymphoproliferative response to phytohemagglutinin ratios implied that HHV-6 infection has some impact on host T-cell immunity during the course of exanthema subitum.

Cell Proliferation↗
PubMed1976

Cellular immune response in vitro: I. A requirement for time-dependent T-lymphocyte cell division of cytotoxic cells in the allogeneic response.

Immunocompetent lymphoid cells cultured in vitro with allogeneic stimulator cells have been shown to produce T-lymphocyte populations which are specifically cytotoxic in vitro to the stimulatory cells whether normal or malignant. Although the culture requirements as well as the allogeneic requirements are known, the events leading to the production of T-lymphocyte cytotoxic cells is poorly understood. This study examines the role of cell division in the production of allogeneic cytotoxic T-cells in vitro. The elimination of cell division during the first 24 hr of allogeneic culture does not affect the cell-mediated cytotoxic immune response in vitro. Cell division is required, however, from 24 hr through 96 hr in culture and not necessary after 96 hr.

Animals↗
PubMed2006

Effect of a Siraitia grosvenori extract containing mogrosides on the cellular immune system of type 1 diabetes mellitus mice.

The purpose of this study was to observe the islet changes of pancreas in insulin-dependent diabetes mellitus (IDDM) mice in comparison to normal mice after application of an extract from Siraitia grosvenori fruits containing mogrosides, in particular, mogroside V. We hypothesized that mogroside extract (MG) attenuates the severity of alloxan-induced IDDM by effects on the immune system. Our data show that IDDM mice exhibited significant injury to pancreatic islets cells, which were atrophic. In addition, alloxan induced a notable increase in the expression of CD8+ lymphocytes to form a dramatic decrease in CD4+/CD8+ ratio (while CD4+ was unchanged). MG, administered to normal and experimental diabetic mice for 4 wk, effectively attenuated the early clinical symptoms, biochemical abnormalities, and pathological damages in pancreatic islets. Furthermore, at low dose, MG regulated the immune imbalance observed in alloxan-induced IDDM mice by up-regulating the CD4+ T-lymphocyte subsets and CD4/CD8 ratio, and altering the intracellular cytokine profiles. The expression of the pro-inflammatory Th1 cytokines: IFN-gamma, TNF-alpha in splenic lymphocytes was altered toward a beneficial Th2 pattern. MG therapy had no effect on normal mice, except that low dosage MG could up-regulate the IL-4 expression levels. The results revealed that MG exhibited antidiabetic effects presumably due to the presence of mogrosides.

Animals↗
PubMed1979

The effect of methanol extraction residue of BCG on the cellular immune response in patients with malignant melanoma.

Twenty-one patients with malignant melanoma stage III and IV were treated by intradermal injections of MER--methanol extraction residue of Baccillus Calmette-Guérin (BCG). Twelve of the patients, all with active disease, received chemotherapy in addition. Tests of skin reactivity to recall antigens and in vitro lymphocyte transformation by phytohemagglutinin (PHA), purified protein derivative (PPD), Canadidine, and Varidase were performed in 19 of the patients before and after the MER therapy. The skin reactivity improved in 8 patients, 5 patients maintained their cutaneous competence, 3 remained incompetent, and in 3 other patients a decrease in reactivity occurred. Improvement or maintenance of cutaneous response was more common in stage III than in stage IV patients. The in vitro lymphocyte stimulation tests have shown that reactivity increased or remained at a high level in 9 of 11 patients in stage III. It dropped or remained low in 2 patients in respect to all antigens used in spite of repeated MER injections. In most patients with stage IV disease no improvement could be detected. MER seems to be a potent immunostimulator in patients in stage III. The side effects were tolerable in all patients and consisted of local reactions and influenza-like symptoms. In 4 patients treated with MER by intralesional injections, transient flattening of nodules occurred but no complete regression was observed.

Adult↗
PubMed1999

Enhancement of cellular immune response in HIV-1 seropositive individuals: A DNA-based trial.

A DNA-based vaccine containing HIV-1 Env and Rev genes was tested for safety and host immune response in 15 HIV-infected asymptomatic patients with CD4-positive lymphocyte counts >/=500/microl of blood and receiving no antiviral therapy. Successive groups of patients received three doses of vaccine at 30, 100, or 300 microg at 10-week intervals in a dose-escalation trial. Some changes were noted in cytotoxic T-lymphocyte activity against gp160-bearing targets. Importantly, enhanced specific lymphocyte proliferative activity against HIV-1 envelope was observed in multiple patients. Three of three patients in the 300-microg dose group also developed increased MIP-1alpha levels which were detectable in their serum. Interestingly patients in the lowest dose group showed no overall changes in the immune parameters measured. The majority of patients who exhibited increases in any immune parameters were contained within the 300 microg, which was the highest dose group. These studies support further investigation of this technology for the production of antigen-specific immune responses in humans.

AIDS Vaccines↗
PubMed2001

Cellular immune response against tropomyosin isoform 5 in ulcerative colitis.

We have reported an autoantibody response in ulcerative colitis (UC) against human tropomyosin isoform 5 (hTM5), the predominant colonic epithelial cell hTM isoform. In this report, we determined the number of IFN-gamma-secreting cells (spot-forming cells, SFC) against hTM5 by an enzyme-linked immunospot (ELISPOT) assay. Another cytoskeletal protein, caldesmon, CaD40, was used as a control antigen. Peripheral blood mononuclear cells were separated by a Ficoll density gradient from 28 patients with UC, 13 patients with Crohn's disease (CD), and 9 healthy subjects (HS). The mean (+/-SEM) SFC values against hTM5 in UC, CD, and HS were 48.8 +/- 8.1, 18.6 +/- 4.6, and 20.8 +/- 8.6, respectively. The value in UC was significantly higher than those in CD (P < 0.005) and HS (P < 0.025). SFC values in CD did not differ from those in HS. None of the 50 samples (except 1 UC) reacted to the CaD40 antigen. This study demonstrates, for the first time, a defined colon epithelial cell antigen, hTM5, that is capable of inducing a significant T cell response in UC but not in CD.

Adolescent↗
PubMed1994

Long-term humoral and cellular immunity after vaccination with cell culture rabies vaccines in man.

To determine the duration of anti-rabies immunity, peripheral blood of 18 vaccinees was obtained between 2 and 14 years after immunization. Peripheral blood mononuclear cells (PBMC) and serum were tested for the presence of either rabies virus-specific antibodies or rabies antigen-specific proliferation. Neutralizing immunoglobulin class G anti-rabies virus antibodies could be detected in sera of all vaccinees, but not in 18 age- and sex-matched controls. Rabies antigen-induced proliferation of PBMCs from vaccinees was significantly higher than that of controls. The anti-rabies T and B cell response showed no time-dependent pattern. These results suggest the induction of a long-term immunity after rabies immunization according to pre- and post-exposure schedules with inactivated cell culture vaccines against rabies.

Adult↗
PubMed2001

UVB irradiation suppresses cytokine production and innate cellular immune functions in mice.

We examined whether ultraviolet-B (UVB) irradiation (6 kJ/m2) alters cytokine production and other innate immune reactions by murine peritoneal macrophages and peripheral neutrophils. Along with these experiments, serum IgG levels were also assessed. In addition, using scanning electron microscopy (SEM) we observed macrophages that had been exposed to UVB in vitro. Results showed that UVB irradiation: (1) decreased IL-12 production while increasing IL-1alpha secretion from macrophages, but had no effect on IL-1alpha from neutrophils; (2) suppressed phagocytosis of macrophages but not of neutrophils; (3) diminished active oxygen production of macrophages but not of neutrophils; (4) had no effect on serum IgG levels; and (5) caused significant cell destruction of macrophages in vitro. These results suggested: (1) that UVB irradiation could induce characteristic suppression of innate immunity; (2) that innate cellular immunity was more susceptible to the effects of UVB irradiation than humoral immunity.

Animals↗
PubMed1999

Cellular immune responses in mice infected with the intestinal nematode Trichuris muris.

CBA and B10.BR mice show variation in immune response to the intestinal nematode Trichuris muris. CBA mice develop strong resistance, eliminating worms from the intestine; B10BR mice are permissive and develop chronic infections. It is already known that resistance and permissiveness reflect differential T helper responses. The data reported here show that resistant CBA mice express good antigen-specific lymphocyte proliferative responses to infection, whereas cells from B10.BR mice are relatively anergic, although still responsive to Concanavalin A (ConA). The possibility that the altered proliferative responsiveness seen in infected B10.BR mice reflected quantitative or qualitative changes in T helper cells was examined by comparing cytokine production and expression of cell surface markers (CD4, CD8, and CD28) in mesenteric lymph node cells and spleen cells from both strains and comparing these with the characteristics of cells from resistant CBA mice and from CBA mice that had been rendered permissive to infection by a combination of irradiation and corticosteroid treatment. As expected, cells from B10.BR mice produced high levels of interferon-gamma (IFN-gamma), whereas those from CBA mice released high levels of IL-5, whether stimulated with adult worm somatic antigens, excretory/secretory antigens, or ConA. Immunosuppressed CBA mice produced high levels of both IFN-gamma and IL-5 throughout the experiment. FACS analysis revealed a decrease of CD4+ and an initial increase in CD8+ cells in all infected mice. No major changes occurred in the relative proportion of CD28(+) cells. Further evaluation of the CD28 costimulatory molecule, measured as mean fluorescence intensity, displayed down-regulation in permissive and immunosuppressed mice. The data obtained suggest that lymphocyte unresponsiveness and permissiveness to T. muris infection may be associated with a down-regulation or an initially reduced expression of costimulatory CD28 molecules.

Animals↗