Abstract
Infection of rhesus monkeys with simian immunodeficiency virus (SIV) is not accompanied by the generation of protective humoral or cellular immune responses to the virus. In an attempt to enhance immunity against SIV, international investigators infected rhesus monkeys with SIV, pulsed dendritic cells from the animals with inactivated SIV, and administered the autologous cells subcutaneously as a primary vaccination followed by 4 booster injections. By 6 weeks after the initial injection, blood SIV cellular DNA decreased by 50-fold and plasma SIV RNA levels were reduced by 1,000-fold. The reduction in viral load appeared to be related to the development of increased numbers of SIV-specific memory T cells and an increased titer of neutralizing antibody. This may be a promising approach for vaccination against human immunodeficiency virus.
Lu W, Wu X, Lu Y, Guo W, Andrieu JM: Therapeutic dendritic-cell vaccine for simian AIDS. Nat Med. 9:27–32, 2003.
Most software used for quantitation of immunohistochemistry relies on color thresholding and pixel counting to generate a semi-quantitative measure of chromagen amount. However, American scientists have developed an algorithm for performing truly quantitative inmmunohistochemistry. This technique can be applied to large areas of histologic sections. The technique has been validated by evaluating immunohistochemical staining of cells expressing different levels of gastrin-releasing peptide receptor and demonstrating that the receptor number determined by quantitative immunohistochemistry was comparable to that determined by binding of radio-labeled ligand. The program developed by these investigators is available online at http://www.uic.edu/com/dom/gastro/Freedownloads.html.
Matkowskyj KA, Cox R, Jensen RT, Benya RV: Quantitative immunohistochemistry by measuring cumulative signal strength accurately measures receptor number. J Histochem Cytochem 51:205–214, 2003.
Alterations in the SAP gene are associated with immunodeficiency in man. To study the function of the gene, researchers produced SAP knockout mice and tested the ability of these mice to produce antibodies to lymphocytic choriomeningitis virus. In both knockout and wild type mice, virus-specific antibody secreting cells (ASC) appeared 8 days after infection then diminished in number over the next few weeks. While the number of ASC in wild type mice eventually stabilized, the number of these cells in knockout mice continued to decline, and knockout mice did not develop long-lived plasma cells or memory B cells. Adoptive transfer studies revealed that the defect lay not in the B cells but in CD4+ T cells. Thus, although SAP is required for the production of long-term humoral immunity, early B-cell help and immunoglobulin class switching occurs normally in the absence of SAP.
Crotty S, Kersh EN, Cannons J, Schwartzberg PL, Ahmed R: SAP is required for generating long-term humoral immunity. Nature. 421:282–287, 2003.
To determine the efficiency of different routes of prion transmission, investigators used transmissible mink encephalopathy in hamsters to compare inoculation at various sites (intracerebral, intrasciatic nerve, intraperitoneal, intramuscular, intravenous, and intratongue) and ingestion. Of the non-neuronal routes, intratongue injection gave the shortest incubation period; this route of infection was 100,000-fold more effective than ingestion. Intratongue inoculation led to regional infection of the lymphoreticular system, and the disease agent was transported to the brain via the hypoglossal nerve. These findings indicate that tongue lesions can enhance the development of prion disease and that use of tongue as a food source may have adverse public health consequences.
Bartz JC, Kincaid AE, Bessen RA: Rapid prion neuroinvasion following tongue infection. J Virol. 77:583–591, 2003.
Xenoantigens synthesized by the enzyme α1,3-galactosyltransferase (α1,3GT) cause hyperacute rejection of pig organs transplanted into humans. A group of scientists has now produced homozygous α1,3GT knockout pigs. These pigs were produced by the novel technique of generating double knockout fibroblasts from fetal fibroblasts obtained from cloned heterozygous α1,3GT knockout animals, selecting for lack of α1,3GT function using toxin A from Clostridium difficile, and generating new pigs by a second round of cloning. These pigs have two advantages for use in xenotransplantation: they lack expression of major xenoantigens and they do not express antibiotic resistance genes.
Phelps CJ, Koike C, Vaught TD, Boone J, Wells KD, Chen SH, Ball S, Specht SM, Polejaeva IA, Monahan JA, Jobst PM, Sharma SB, Lamborn AE, Garst AS, Moore M, Demetris AJ, Rudert WA, Bottino R, Bertera S, Trucco M, Starzl TE, Dai Y, Ayares DL: Production of alpha 1,3-galactosyltransferase-deficient pigs. Science 299:411–414, 2003.