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Transplantation. 2002 Sep 15;74(5):722-32.
Characterization of cytotoxic function of CMV-pp65-specific CD8+ T-lymphocytes identified by HLA tetramers in recipients and donors of stem-cell transplants.

Lacey SF, Gallez-Hawkins G, Crooks M, Martinez J, Senitzer D, Forman SJ, Spielberger R, Zaia JA, Diamond DJ.

Laboratory of Vaccine Research, Division of Virology, Beckman Research Institute of the City of Hope, Duarte, California 91010, USA. slaceoh.org

BACKGROUND: Human cytomegalovirus (CMV) is a ubiquitous herpesvirus that is an important complication of bone marrow and allogeneic stem-cell transplant (HSCT). CD8 T-lymphocytes have an important role in immunity against CMV, but correlation between antigen-specific subpopulations of these cells and protection are still unclear. METHODS: Flow analysis with fluorescently-conjugated human leukocyte antigen (HLA) class I tetramers (Tet) was used to investigate levels of CMV-specific CD8 T-lymphocytes in peripheral blood monocyte cells (PBMC) samples from HSCT donors and recipients and their ability to produce interferon (IFN)-gamma on stimulation with either CMV antigenic peptide or nonspecific mitogenic stimulation. Chromium release assays were used to evaluate ex vivo CMV-specific cytotoxicity associated with the PBMC samples. RESULTS: Use of Tet in conjunction with fluorescently conjugated anti-T-cell receptor (TCR) beta-chain variable (Vbeta) monoclonal antibodies indicated that the Vbeta repertoires associated with Tet cells seen in two HSCT recipients were similar to the Vbeta repertoires of the Tet cells in their HSCT donors. Significant ex vivo cytotoxicity against peptide-loaded targets was measured from several recipient samples after transplant. However, PBMC from the HSCT donors, even when containing populations of CMV-specific Tet cells capable of secreting IFN-gamma in response to peptide stimulation, possessed no ex vivo CMV-specific cytotoxicity. CONCLUSIONS: We hypothesize that in the setting of the reconstituting immune system of HSCT recipients, CMV reactivation may stimulate a functional change in CMV-specific CD8 T-lymphocytes, rendering them able to directly lyse target cells presenting CMV antigens without in vitro stimulation. These findings have important implications for development of vaccines designed to induce protective cellular immunity to CMV in transplant recipients.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12352893&dopt=Abstract

Vaccine. 2003 Jan 30;21(7-8):809-11.
Targeting of plant-derived vaccine antigens to immunoresponsive mucosal sites.

Rigano MM, Sala F, Arntzen CJ, Walmsley AM.

Department of Plant Biology, Arizona State University, 85215, Tempe, AZ, USA

Most pathogenic microorganisms enter their host via the mucosal surfaces lining the digestive, respiratory and urino-reproductive tracts of the body. The most efficient means of protecting these surfaces is through mucosal immunization. Transgenic plants are safe and inexpensive vehicles to produce and mucosally deliver protective antigens. However, the application of this technology is limited by the poor response of the immune system to non-particulate, subunit vaccines. Co-delivery of therapeutic proteins with targeting proteins, such as the B subunit of the Escherichia coli heat labile enterotoxin (LTB), could increase the effectiveness of such antigens.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12531365&dopt=Abstract [PubMed - in process]

Mol Cell Biol. 2003 Jan;23(1):272-9.
Carcinoembryonic antigen-related cell adhesion molecule 10 expressed specifically early in pregnancy in the decidua is dispensable for normal murine development.

Finkenzeller D, Fischer B, Lutz S, Schrewe H, Shimizu T, Zimmermann W.

Institute of Molecular Medicine and Cell Research, University of Freiburg, Germany.

The carcinoembryonic antigen (CEA) family consists of a large group of evolutionarily and structurally divergent glycoproteins. The murine CEACAM9 and CEACAM11-related proteins as well as the pregnancy-specific glycoproteins (PSG) are secreted members of the CEA family which are differentially expressed in fetal trophoblast cell populations during placental development. PSG are essential for a successful pregnancy, possibly by protecting the semiallotypic fetus from the maternal immune system. In contrast, Ceacam10 mRNA, coding for a protein identical in structure with CEACAM11-related proteins, is expressed in the maternal decidua surrounding the implantation site of the conceptus only during early stages of gestation between day 6.5 and day 10.5 postcoitum. To determine its role during murine development, we inactivated Ceacam10. Ceacam10(-/-) mice developed, like the previously established Ceacam9(-/-) mice, indistinguishably from wild-type littermates with respect to sex ratio, weight gain, and fertility. However, a small but significant reduction of the litter size by 23% was observed in Ceacam10(-/-) matings. Furthermore, combining the Ceacam9 and Ceacam10 null alleles, both located on chromosome 7, by meiotic recombination and subsequent mating of heterozygotes carrying both knockout alleles on one chromosome yielded wild-type and double knockout offspring at the expected Mendelian ratio. Taken together, both Ceacam10 and Ceacam9, alone or in combination, are not essential for either murine placental and embryonic development or for adult life.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12482980&dopt=Abstract

Nature. 2002 Sep 26;419(6905):395-9.
Pleiotropic defects in lymphocyte activation caused by caspase-8 mutations lead to human immunodeficiency.

Chun HJ, Zheng L, Ahmad M, Wang J, Speirs CK, Siegel RM, Dale JK, Puck J, Davis J, Hall CG, Skoda-Smith S, Atkinson TP, Straus SE, Lenardo MJ.

Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.

Apoptosis is a form of programmed cell death that is controlled by aspartate-specific cysteine proteases called caspases. In the immune system, apoptosis counters the proliferation of lymphocytes to achieve a homeostatic balance, which allows potent responses to pathogens but avoids autoimmunity. The CD95 (Fas, Apo-1) receptor triggers lymphocyte apoptosis by recruiting Fas-associated death domain (FADD), caspase-8 and caspase-10 proteins into a death-inducing signalling complex. Heterozygous mutations in CD95, CD95 ligand or caspase-10 underlie most cases of autoimmune lymphoproliferative syndrome (ALPS), a human disorder that is characterized by defective lymphocyte apoptosis, lymphadenopathy, splenomegaly and autoimmunity. Mutations in caspase-8 have not been described in ALPS, and homozygous caspase-8 deficiency causes embryonic lethality in mice. Here we describe a human kindred with an inherited genetic deficiency of caspase-8. Homozygous individuals manifest defective lymphocyte apoptosis and homeostasis but, unlike individuals affected with ALPS, also have defects in their activation of T lymphocytes, B lymphocytes and natural killer cells, which leads to immunodeficiency. Thus, caspase-8 deficiency in humans is compatible with normal development and shows that caspase-8 has a postnatal role in immune activation of naive lymphocytes.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12353035&dopt=Abstract

Dev Immunol. 2002 Mar;9(1):9-17.
Maternal modulation of neonatal immune system development.

Fagoaga OR, Nehlsen-Cannarella SL.

Department of Pathology, Immunology Center, Loma Linda University School of Medicine and Medical Center, CA 92354-2870, USA.

Changes in programming of neonatal immune development were effected through maternal immune modulation (Leishmania major inoculation). In progeny of these dams, immune profiles in both blood and spleen were changed throughout the neonatal period and were pronounced after weaning. White blood cell (WBC) and lymphocyte counts in blood of 45-day-old progeny were two-fold less than control animals. In blood, proportions of B cells were greater, while T helpers, Tc/s and NK cells were less than in controls. In contrast, proportions of splenic B and NK cells were greater than controls. But, proportions of all T and Tc/s cells on d20 and 45 were lower than controls. In blood, absolute numbers of all T, Th naive and Th memory cells were lower than in controls. In contrast, in the spleen, numbers of NK, T and Th naive and memory cells were up to 200% greater than in control pups. Cytokine responses of splenic lymphocytes stimulated through CD3 ligation revealed no difference in IL-4 production. In contrast, IL-2 and IFNgamma were lower on d45 and 5, respectively, in the experimental compared to control mice. These data support the hypothesis that maternal immune events during gestation can modulate the pattern of immune development in offspring.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12353663&dopt=Abstract

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