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PubMed1993

CD45RA+ T cells: not simple virgins.

1. The T cells which mediate immunological memory remain elusive. Identification of such cells would open the door to increasingly specific immunotherapy in areas such as transplantation and autoimmunity. 2. Over the last few years attempts have been made to identify phenotypic markers which can distinguish naive or virgin T cells from primed or memory ones. In humans, great hopes were raised when it was shown that the level of expression of the higher-molecular-mass isoforms (CD45RA) of the tyrosine phosphatase, CD45, correlated with previous exposure to antigen. 4. However, our studies in the mouse and more recent studies in rat and human suggest that expression of CD45RA more closely correlates with the state of responsiveness of the T cell. 5. Thus, with time, activated/memory T cells return to a state of quiescence or hypo-responsiveness and express high levels of CD45RA. Hence, not all CD45RA+ T cells are virgins.

Aging↗

PubMed2006

Immunotherapeutic relief from persistent infections and amyloid disorders.

Persistent infections and amyloid disorders afflict a significant number of people worldwide. It would appear at first glance that the treatment of these afflictions should be entirely unrelated; however, in both cases components of the adaptive immune system have been harnessed in an attempt to provide some therapeutic relief. Given that the ability of a pathogen to establish persistence often depends in part on a shortcoming of the adaptive immune response, it seems logical to devise immunotherapies with the intention of supplementing (or replacing) the insufficient immunologic element. A case in point is an intervention referred as immunocytotherapy, which relies upon the adoptive transfer of pathogen-specific T lymphocytes into a persistently infected host. Remarkably, the adoptively transferred T lymphocytes not only have the capacity to clear the persistent infection, but can also provide the recipient with protection against subsequent rechallenge (i.e., immunologic memory). Treatment of amyloid disorders (e.g., Alzheimer disease, sporadic inclusion-body myositis) with a similar therapeutic approach is complicated by the fact that the aberrant protein accumulations are self-derived. Focusing the adaptive response on these aberrant self-proteins has the potential to result in autoimmune pathology. This review critically evaluates the importance of immunotherapeutic approaches for the treatment of persistent infections and amyloid disorders, and attempts to delineate the interventions that are most likely to succeed in an exceedingly complex disorder such as sporadic inclusion-body myositis.

Alzheimer Disease↗

PubMed1984

Immune response to different tick-borne encephalitis vaccines as revealed by lymphocyte blast transformation and virus neutralization tests.

Immunological memory has been demonstrated in lymphocytes of persons vaccinated against tick-borne encephalitis (TBE). Stimulation indices (SI) of lymphocytes in response to TBE virus antigens in lymphocyte blast transformation test increased after complete vaccination course with the commercial vaccine; by this time, sera of vaccinees contained virus neutralizing antibodies. The concentrated purified vaccine had a higher immunogenic activity, as evidenced by increased SI and virus neutralizing antibodies (NA) in the vaccinated subjects already after the first and second vaccinations.

Adolescent↗

PubMedDate not supplied

[Production of interleukin-2 in vitro and in vivo in elderly people, vaccinated with live and inactivated flu vaccines separately and combined].

Forty-three elderly individuals were immunized with Russian trivalent live cold-adapted influenza vaccine (LIV) and US trivalent influenza vaccine (IIV) administered separately or in combination. IL-2 production in vitro (in supernatants of cultures of lymphocytes stimulated with homologous viral antigens and PHA) and in vivo (in blood serum) and other factors of specific antiinfluenza immunity were compared. Vaccination of elderly subjects with commercial vaccines induced T-helper immunological memory, which manifests by increased secretion of IL-2 in vitro and in vivo. Simultaneous vaccination with LIV + IIV and revaccination (in 1 month) with LIV was the most effective method stimulating IL-2 production. The levels of IL-2 production in vitro were in good correlation with the secretion of this cytokin in vivo, lymph proliferation, and serum antibody production. No correlation between IL-2 production in vitro and the formation of local immune response (IgA in nasal swabs) was detected.

Aged↗

PubMed2000

The abrogation of allosensitization following the induction of mixed allogeneic chimerism.

The association of preformed anti-donor Abs with the hyperacute rejection of bone marrow and solid organ allografts and the persistence of the anti-donor immune response secondary to immunologic memory make allosensitization an absolute contraindication to transplantation. Mixed allogeneic (A + B-->A) bone marrow chimerism has been demonstrated to confer donor-specific tolerance in nonsensitized recipients, but has not been evaluated in the setting of allosensitization. The current study documents that despite significant anti-donor sensitization, mixed allogeneic engraftment is possible and provides a marked advantage over fully allogeneic (B-->A) models. Moreover, the acceptance of donor skin grafts and loss of circulating anti-donor Abs suggest that allosensitization can be abrogated with the induction of stable mixed allogeneic chimerism.

Animals↗

PubMed1996

Gene gun-mediated skin transfection with interleukin 12 gene results in regression of established primary and metastatic murine tumors.

Particle-mediated (gene gun) in vivo delivery of the murine interleukin 12 (IL-12) gene in an expression plasmid was evaluated for antitumor activity. Transfer of IL-12 cDNA into epidermal cells overlying an implanted intradermal tumor resulted in detectable levels (266.0 +/- 27.8 pg) of the transgenic protein at the skin tissue treatment site. Despite these low levels of transgenic IL-12, complete regression of established tumors (0.4-0.8 cm in diameter) was achieved in mice bearing Renca, MethA, SA-1, or L5178Y syngeneic tumors. Only one to four treatments with IL-12 cDNA-coated particles, starting on day 7 after tumor cell implantation, were required to achieve complete tumor regression. This antitumor effect was CD8+ T cell-dependent and led to the generation of tumor-specific immunological memory. By using a metastatic P815 tumor model, we further showed that a delivery of IL-12 cDNA into the skin overlying an advanced intradermal tumor, followed by tumor excision and three additional IL-12 gene transfections, could significantly inhibit systemic metastases, resulting in extended survival of test mice. These results suggest that gene gun-mediated in vivo delivery of IL-12 cDNA should be further developed for potential clinical testing as an approach for human cancer gene therapy.

Animals↗

PubMed1994

Regulation of IgG antibody titers by the amount persisting of immune-complexed antigen.

Antigens normally induce an immunoglobulin (Ig)G response which stays at an elevated level for several weeks or months, constituting an important part of the immunological memory. This study investigated factors influencing the level of neutralizing IgG titers against a virus and shows that within the range tested it was independent of the number of initially available and potentially responding T helper and B cells, but was regulated by the amount of specific IgG-immune complexes forming depots of persisting antigen. These findings support the notion that the efficiency of vaccines in inducing long-lasting protective IgG is regulated predominantly by the amount of persisting (and presumably follicular dendritic cell-associated) antigen-antibody complexes.

Animals↗

PubMed2002

Modulation of delayed-type hypersensitivity and acquired cellular resistance by orally administered viable indigenous lactobacilli in Listeria monocytogenes infected Wistar rats.

AIMS: Various probiotic lactobacilli have been reported to modulate immunity. In this study we investigate the effects of viable indigenous Lactobacillus strains Utr-1, Utr-2 and Utr-3, on T cell-mediated immunological memory responses. METHODS AND RESULTS: In Listeria monocytogenes infected rats it was demonstrated that short-term daily ingestion of Lactobacillus strain Utr-3 significantly decreased delayed-type hypersensitivity (DTH) expression, whereas long-term, daily oral administration of Lactobacillus strain Utr-3 and Lactobacillus strain Utr-2 significantly enhanced acquired cellular resistance (ACR) towards Listeria re-infection. CONCLUSIONS: Our findings demonstrate that certain indigenous Lactobacillus strains are capable of modulating T cell-mediated immunity. SIGNIFICANCE AND IMPACT OF THE STUDY: Our results support the importance of indigenous microflora analysis in probiotic lactobacilli studies.

Administration, Oral↗

PubMed1982

Immune response mediated by liposome-associated protein antigens. I. Potentiation of the plaque-forming cell response.

Mice, immunized with liposome-associated bovine serum albumin (LSM-BSA), showed a significantly higher BSA-specific plaque-forming cell (PFC) response than did mice injected with fluid BSA (fBSA). Physical association between the liposome carrier and the protein antigen is imperative for potentiating the PFC response, since the injection of empty liposomes, together with fBSA, was found to be ineffective in inducing an immune response. Liposome-associated protein antigen was found to be a potent stimulator of immunological memory, as demonstrated by the ability of LSM-BSA primed animals to generate a vigorous PFC response upon challenge with the weakly immunogenic fBSA. The injection of congenitally athymic homozygous nude (Nu/Nu) mice with LSM-BSA failed to induce significant antibody formation, whereas the heterozygous (Nu/+) littermates gave a normal PFC response to the same LSM-BSA preparation. Thus, BSA remains a T-cell-dependent antigen, despite its entrapment within liposomes, and T lymphocytes appear to play an obligatory role in providing synergistic interactions for eliciting a BSA-specific PFC response to the LSM-BSA.

Animals↗

PubMed1997

Protective antibodies and anamnestic response in Salvelinus fontinalis to Cryptobia salmositica and innate resistance of Salvelinus namaycush to the hemoflagellate.

Cryptobia-susceptible Salvelinus fontinalis vaccinated with a live Cryptobia salmositica vaccine were protected against C. salmositica and they were still protected 53 wk after their initial challenge. Parasites were lysed when they were incubated with immune plasma and complement and this confirms that complement-fixing antibody is an important part of the protective mechanism. Immunological memory was demonstrated in both vaccinated-challenged, and infected-recovered S. fontinalis as there were rapid and significant increases in complement-fixing antibody titers after parasite challenge. This indicates that S. fontinalis are capable of an anamnestic response. Most naive Salvelinus namaycush were not susceptible to C. salmositica infection, and their fresh plasma lysed C. salmositica under in vitro conditions. The lytic factor(s) was inactivated by heating the plasma prior to parasite incubation. This indicates that the alternate pathway of complement activation is likely the mechanism of innate resistance in S. namaycush.

Animals↗

PubMed2005

Prevention of hepatitis B in nonresponders to initial hepatitis B virus vaccination.

Although vaccination against hepatitis B virus (HBV) is highly successful, 5% to 10% of individuals do not experience a response with an adequate antibody level to hepatitis B surface antigen (anti-HBs). Contributing causes for nonresponse to the vaccine are genetic predisposition, immunosuppression, and certain chronic illnesses. The distinction between true nonresponse (after adequate immunization) and waning anti-HBs levels is important. The latter is not uncommon in populations in areas of the world with low endemicity for HBV infection. Data from subjects with waning anti-HBs levels show that immunologic memory may still protect these individuals against acute HBV infection or may prevent chronic infection with HBV for < or =10 years after immunization. Recent reports from Asia and Alaska describe cases of chronic HBV infection 15 years after immunization in subjects who have very low levels of anti-HBs. Thus, nonresponders or those with waning immunity who may be at risk of HBV infection in subsequent years may require a booster dose. Clinical algorithms to reimmunize nonresponders have been described and are discussed in this article. Experimental hepatitis B vaccines have shown some promise in nonresponders but are not commercially available in the United States.

Hepatitis B↗

PubMed1984

Mucosal antitoxic and antibacterial immunity after cholera disease and after immunization with a combined B subunit-whole cell vaccine.

Mucosal and systemic immune responses to a new oral cholera vaccine, consisting of the B subunit plus killed vibrios, were studied in Bangladeshi volunteers and compared with those to clinical cholera. A single peroral dose of vaccine induced a local IgA antitoxin response in intestinal-lavage fluid of seven of eight vaccinees; the response closely mimicked that of patients convalescing from cholera, and evidence of the induction of local immunologic memory was found as well. Two peroral doses were needed for stimulation of an intestinal IgA immune response to the lipopolysaccharide of Vibrio cholerae that was comparable to the response obtained after clinical cholera. This response to peroral immunization was considerably stronger than that to parenteral vaccination, although the intramuscular route gave rise to the strongest IgG antitoxin and antilipolysaccharide responses in serum. The results suggest that B subunit-whole cell vaccine, when given in at least two oral doses, may be a good candidate for use in cholera prophylaxis.

Administration, Oral↗

PubMed1999

[Neisseria meningitidis and meningitis].

Meningococcal meningitis epidemics can occur anywhere in the world. However this risk is particularly high during the dry season in the sub-Saharan zone of Africa known as the Lapeyssonnie meningitis belt. This area characterized by hyperendemicity that regularly gives rise to epidemics. Multilocus enzyme electrophoresis has made possible identification and monitoring of the progression of virulent clones of Neisseria meningitidis strains in the world. Monitoring is now possible by multilocus sequence typing and data bank on the Internet. Vaccination is a major prophylactic modality. The usefulness of plain group A plus C polysaccharide vaccines is limited because of poor effectiveness in young children who constitute the highest risk group. During epidemics, mass vaccination should be carried out as early as possible according to the state of alert defined for the area. More recent conjugate vaccines against group A and C, which are effective in young children and provide long-term protection by induction of immunologic memory, may allow routine vaccination in the future. Although clinical signs are often apparent, not all cases are diagnosed by clinical examination unless gravity is taken into account. Untreated the disease is always fatal. The only hope of survival is early institution of appropriate antimicrobial therapy (even prior to hospitalization). Several strains resistant to chloramphenicol have been reported and the number of strains with reduced sensitivity to penicillin is rising constantly. Although treatment remains feasible, the existence of resistant forms raises the need to monitor the sensitivity of meningococci using standardized of antibiograms.

Adult↗

PubMed1981

The goldfish immune response. I. Characterization of the humoral response to particulate antigens.

Anti-red blood cells (RBC) and anti-hapten antibody synthesis were studied in the goldfish, Carassius auratus. Spontaneous haemagglutination titres were found against all the antigens tested. A weak secondary response was observed in RBC-primed fish boosted during the end-phase of the primary antibody production. However, when the second antigenic challenge was performed during the early exponential phase of a primary stimulation, an important amplified response was obtained. The antibody production and immunological memory can be dissociated: no antibody synthesis occurred in glutaraldehyde-fixed RBC (F-RBC) primed was obtained when untreated or F-RBC were given to F-RBC primed animals. The amplified response to sheep red blood cells (SRBC) was significantly inhibited when fish were primed with a mixture of SRBC and Xenopus red blood cells (XRBC), demonstrating an antigenic competition phenomenon. Studies on anti-trinitrobenzene responses confirm the efficiency of E. coli lipopolysaccharide as a carrier for fish anti-hapten immunization. The kinetics and regulation of antibody synthesis in fish are discussed in relation to the described results.

Animals↗

PubMed2000

C-C chemokine-encoding DNA vaccines enhance breakdown of tolerance to their gene products and treat ongoing adjuvant arthritis.

Depending on the method of immunization, a single administration of CFA may result in the development of a local inflammatory process or chronic polyadjuvant-induced arthritis (AA). We administered naked DNA vaccines encoding MIP-1 alpha, MCP-1, MIP-1 beta, and RANTES to Lewis rats and confirmed that each of these vaccines induced immunological memory to the corresponding gene product. Upon induction of disease, this memory effectively inhibited the development of the autoimmune condition. Self-specific Ab's developed in DNA-vaccinated animals were neutralizing in vitro and could adoptively transfer the beneficial effect of each vaccine. Repeated administration of the constructs encoding MCP-1, MIP-1 alpha, or RANTES inhibited the development and progression of AA, even when each vaccine was administered only after the onset of disease. This suggests a highly effective way by which the immune system could be re-educated to generate protective immunity against its own harmful activities.

Animals↗

PubMed1988

T-cell subsets in delayed-type hypersensitivity, protection, and granuloma formation in primary and secondary Listeria infection in mice: superior role of Lyt-2+ cells in acquired immunity.

Immunity to Listeria monocytogenes was studied in mice treated with rat monoclonal antibodies (MAbs) specific for the Thy-1.2, L3T4, and Lyt-2 T-cell markers. Three characteristic T-cell-mediated phenomena were investigated. Delayed-type hypersensitivity (DTH) to listerial antigen was totally abolished in mice treated with anti-Thy-1.2 or anti-L3T4 MAbs, whereas anti-Lyt-2 MAb treatment had no effect, regardless of whether the MAb was given during the induction or the expression of DTH. On the other hand, the elimination of bacteria from the spleens of infected animals was inhibited only by the application of either anti-Thy-1.2 MAb or anti-Lyt-2 MAb. This could be shown most impressively during the secondary infection of immune mice with a normally lethal dose of listeriae. In this situation, treatment with anti-Lyt-2 MAb sufficed to completely abolish immunologic memory, whereas anti-L3T4 MAb had only a marginal effect on antibacterial protection. However, the accelerated development of mononuclear cell foci in the livers of immune mice was inhibited by the application of both anti-L3T4 MAb and anti-Lyt-2 MAb. It is concluded that in murine listeriosis, DTH and acquired immunity to reinfection are dissociable phenomena. Although DTH is a function of L3T4+ T lymphocytes, Lyt-2+ T cells are necessary and sufficient for the expression of acquired resistance to L. monocytogenes. The roles of the different T-cell subsets in granuloma formation warrant further investigation.

Animals↗

PubMed1988

HIV-specific T lymphocyte immunity in mice immunized with a recombinant vaccinia virus.

Infection by the human immunodeficiency virus (HIV) induces T cell immunity in humans, chimpanzees and macaques. The protective value of this immune response is not clear. We have consequently developed a murine experimental system to study HIV-specific CD4 and CD8 T lymphocyte immunity in vitro and in vivo. BALB/c, DBA/2 and C3H/He mice were immunized with vaccinia virus (VV) recombinant VV-11.39 which expresses the gp160 glycoprotein of HIV-1. Primary and secondary cytotoxic T lymphocyte response to HIV were detected with histocompatible mouse target cells transfected with the HIV-1 env gene. Killer cells were positive for the Thy-1 and Ly-2 (CD8) T cell markers, and were restricted by class I H-2 histocompatibility antigens. Immunological memory specific for HIV-1 envelope antigens was clearly induced by vaccination with VV-11.39:spleen cells from mice vaccinated 4 weeks or more prior to assay generated CD4 and CD8 T lymphocyte responses following stimulation in vitro with HIV envelope antigens. The intensity of these responses increased with consecutive vaccinations, indicating that HIV-specific precursor T cell pools were progressively amplified. Finally, DBA/2 mice vaccinated with VV-11.39 developed protective immunity against a syngeneic tumor which expresses HIV-1 env antigens, leading to accelerated tumor rejection and increased survival.

Animals↗

PubMed1973

Maturation of B lymphocytes in the rat. I. Migration pattern, tissue distribution, and turnover rate of unprimed and primed B lymphocytes involved in the adoptive antidinitrophenyl response.

The migration pattern, tissue distribution, and turnover rate of unprimed and primed B lymphocytes involved in the adoptive anti-DNP response was studied. The adoptive primary response restored by unprimed spleen or thoracic duct cells passaged through an intermediate host (intravenous injection and subsequent collection in the thoracic duct lymph) was markedly diminished as compared with that restored by unpassaged cells. On the other hand, the adoptive response restored by passaged spleen or thoracic duct cells from DNP-primed donors was greater than or the same as that restored with unpassaged cells, respectively. This suggests that unprimed B cells change from nonrecirculating to recirculating lymphocytes after exposure to antigen. Studies of the adoptive anti-DNP response restored by unprimed or primed bone marrow cells showed little change in the time-course or amplitude of the response restored by either population of cells. The relative inability of marrow cells to carry immunological memory was related to the inability of recirculating memory cells to penetrate the marrow. The turnover rate of unprimed and primed B cells was investigated by treating the cell donors with [(3)H]thymidine for 48 h before removal of thoracic duct or spleen cells. The adoptive anti-DNP response restored by unprimed or primed cells was not affected by [(3)H]thymidine treatment. This indicates that both populations of cells turn over slowly. However, our previous studies show that unprimed B cells involved in the adoptive antibody response to ferritin turn over rapidly. The different findings are discussed in the context of antigen-dependent B-cell maturation.

Animals↗