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Immunological values for 562 factory workers from Wonji, Ethiopia, a sugar estate 114 km southeast of the capital city, Addis Ababa, Ethiopia, were compared to values for 218 subjects from Akaki, Ethiopia, a suburb of Addis Ababa, for whom partial data were previously published. The following markers were measured: lymphocytes, T cells, B cells, NK cells, CD4(+) T cells, and CD8(+) T cells. A more in depth comparison was also made between Akaki and Wonji subjects. For this purpose, various differentiation and activation marker (CD45RA, CD27, HLA-DR, and CD38) expressions on CD4(+) and CD8(+) T cells were studied in 60 male, human immunodeficiency virus-negative subjects (30 from each site). Data were also compared with Dutch blood donor control values. The results confirmed that Ethiopians have significantly decreased CD4(+) T-cell counts and highly activated immune status, independent of the geographic locale studied. They also showed that male subjects from Akaki have significantly higher CD8(+) T-cell counts, resulting in a proportional increase in each of the CD8(+) T-cell compartments studied: naïve (CD45RA(+)CD27(+)), memory (CD45RA(-)CD27(+)), cytotoxic effector (CD45RA(+)CD27(-)), memory/effector (CD45RA(-)CD27(-)), activated (HLA-DR(+)CD38(+)), and resting (HLA-DR(-)CD38(-)). No expansion of a specific functional subset was observed. Endemic infection or higher immune activation is thus not a likely cause of the higher CD8 counts in the Akaki subjects. The data confirm and extend earlier observations and suggest that, although most lymphocyte subsets are comparable between the two geographical locales, there are also differences. Thus, care should be taken in extrapolating immunological reference values from one population group to another.

T-cell proliferation is an important in vitro parameter of in vivo immune function and has been used as a prognostic marker of human immunodeficiency virus type 1 (HIV-1) disease progression. The proliferative capacity of T cells in response to various stimuli is commonly determined by a radioactive assay based on incorporation of [(3)H]thymidine ([(3)H]TdR) into newly generated DNA. In order to assess techniques for application in laboratories where radioactive facilities are not present, two alternative methods were tested and compared to the [(3)H]TdR assay as a "gold standard." As an alternative, T-cell proliferation was measured by flow cytometric assessment of CD38 expression on T cells and by an enzyme-linked immunosorbent assay (ELISA) based on bromo-2'-deoxyuridine (BrdU) incorporation. Peripheral blood mononuclear cells (PBMCs), either in whole blood or Ficoll-Isopaque separated, from a total of 26 HIV-1-positive and 18 HIV-1-negative Dutch individuals were stimulated with CD3 monoclonal antibody (MAb) alone, a combination of CD3 and CD28 MAbs, or phytohemagglutinin. BrdU incorporation after 3 days of stimulation with a combination of CD3 and CD28 MAbs correlated excellently with the [(3)H]TdR incorporation in both study groups (HIV-1 positives, r = 0.96; HIV-1 negatives, r = 0.83). A significant correlation of absolute numbers of T cells expressing CD38 with [(3)H]TdR incorporation, both in HIV-1-positive (r = 0.96) and HIV-1-negative (r = 0.84) individuals, was also observed under these conditions. The results of this study indicate that determination of both the number of CD38-positive T cells and BrdU incorporation can be used as alternative techniques to measure the in vitro T-cell proliferative capacity. The measurement of CD38 expression on T cells provides the additional possibility to further characterize the proliferating T-cell subsets for expression of other surface markers.

We recently showed that circulating human CD8⁺ effector cells have a CD45RA⁺CD27^- membrane phenotype. In itself this phenotype appeared to pose a paradox: CD45RA, a marker expressed by unprimed cells, combined with absence of CD27, characteristic for chronically stimulated T cells. To investigate whether differentiation towards the CD45RA⁺CD27^- phenotype is dependent on antigenic stimulation and involves cellular division, TCR V_β usage and telomeric restriction fragment (TRF) length were analyzed within distinct peripheral blood CD8⁺ subsets. FACS analysis showed that the TCR V_β repertoire of CD8⁺CD45RA⁺CD27^- cells differed significantly from that of unprimed CD8⁺CD45RA⁺CD27⁺ cells. Moreover, in two out of six individuals large expansions of particular V_β families were observed in the CD8⁺CD45RA⁺CD27^- subset. CDR3 spectrotyping and single-strand confirmation analysis revealed that within the CD8⁺CD45RA⁺CD27^- population most of the 22 tested V_β families were dominated by oligoclonal expansions. The mean TRF length was found to be 2.3 ± 1.0 kb shorter in the CD8⁺CD45RA⁺CD27^- subset compared with the unprimed CD8⁺CD45RA⁺CD27⁺ population, but did not differ substantially from that of memory type, CD8⁺CD45RA^-CD27⁺ T cells. These findings indicate that the CD8⁺CD45RA⁺CD27^- cytotoxic effector population consists of antigen-induced, clonally expanded cells and confirm that the expression of CD45RA is not a strict marker of antigen non-experienced T cells.

We recently showed that circulating human CD8(+) effector cells have a CD45RA+CD27(-) membrane phenotype. In itself this phenotype appeared to pose a paradox: CD45RA, a marker expressed by unprimed cells, combined with absence of CD27, characteristic for chronically stimulated T cells. To investigate whether differentiation towards the CD45RA+CD27(-) phenotype is dependent on antigenic stimulation and involves cellular division, TCR Vbeta usage and telomeric restriction fragment (TRF) length were analyzed within distinct peripheral blood CD8(+) subsets. FACS analysis showed that the TCR Vbeta repertoire of CD8(+)CD45RA+CD27(-) cells differed significantly from that of unprimed CD8(+)CD45RA+CD27(+) cells. Moreover, in two out of six individuals large expansions of particular Vbeta families were observed in the CD8(+)CD45RA+CD27(-) subset. CDR3 spectrotyping and single-strand confirmation analysis revealed that within the CD8(+)CD45RA+CD27(-) population most of the 22 tested Vbeta families were dominated by oligoclonal expansions. The mean TRF length was found to be 2.3+/-1.0 kb shorter in the CD8(+)CD45RA+CD27(-) subset compared with the unprimed CD8(+)CD45RA+CD27(+) population, but did not differ substantially from that of memory type, CD8(+)CD45RA-CD27(+) T cells. These findings indicate that the CD8(+)CD45RA+CD27(-) cytotoxic effector population consists of antigen-induced, clonally expanded cells and confirm that the expression of CD45RA is not a strict marker of antigen non-experienced T cells.

Within the last 15 years, exceptional progress has been made in the experimental study of solid surfaces. Detailed surface-spectroscopic informa. tion is now available on a wide range of surfaces, with semiconductor and transition metal surfaces studied most.1 In response to this experimental effort a later-starting - but at present equally vigorous - theoretical effort has been undertaken.2

Hintergund: Es wurde der Einfluß einer von Internisten und Strahlentherapeuten der Universität Rostock Mitte 1986 beschlossenen Reduktion der Bestrahlungsdosis bei der Behandlung der Lymphogranulomatose auf die Inzidenz der radiogenen Pneumonitis, Lungenfibrose und Perikarditis nach Mediastinalbestrahlung überprüft. Patienten und Methoden: Im Beobachtungszeitraum von 1983 bis 1992 führten wir bei insgesamt 141 Patienten mit Morbus Hodgkin eine Mediastinalbestrahlung durch, 126 Patienten davon erhielten vor Bestrahlung eine Polychemotherapie (in der Mehrzahl fünf oder mehr Zyklen). Mitte 1986 erfolgte eine Reduktion der Bestrahlungsdosis sowohl bei alleiniger Radiatio (befallene Lymphknotenstationen von 45 Gy auf 40 Gy sowie nichtbefallene Lymphknotenstationen von 40 Gy auf 36 Gy) als auch nach Polychemotherapie (befallene Lymphknotenstationen von 40 Gy auf 36 Gy sowie nichtbefallene Lymphknotenstationen von 36 Gy auf 30 Gy). Vor Dosisreduktion wurde bei 46 Patienten und nach Dosisreduktion bei 95 Patienten eine Mediastinalbestrahlung durchgeführt. Strahlentherapeutisch kamen 60-Kobalt-Gammastrahlung, 15-MV- und 9-MV-Röntgen-Bremsstrahlung sowie 15-MeV- und 9-MeV-Elektronenstrahlung zur Anwendung. Diagnostische. Methode war hauptsächlich die Röntgenthoraxübersichtsaufnahme in zwei Ebenen, in Einzelfällen wurden thorakale Computertomographie, Elektrokardiographie und Echokardiographie genutzt. Ergebnisse: Im gesamten Untersuchungszeitraum von 1983 bis 1992 wurde nach Mediastinalbestrahlung in 31% eine Pneumonitis, in 16% eine Lungenfibrose und in 10% eine Perikarditis diagnostiziert. Nach Reduktion der Bestrahlungsdosis verringerten sich die Pneumonitisrate von 35% auf 24% (erreicht annähernd das Signifikanzniveau von p<0,05), die Lungenfibroserate von 24% auf 12% (signifikant mit p<0,05) und die Perikarditisrate von 26% auf 2,1% (signifikant mit p<0,01). Kumulatives Gesamtüberleben und rezidivfreies Überleben verschlechterten sich durch die Reduktion der Bestrahlungsdosis nicht. Schlußfolgerungen: Die Reduktion der Bestrahlungsdosis bei der Behandlung der Lymphogranulomatose hat sich aufgrund der Verringerung der Nebenwirkungsraten bei vergleichbaren Therapieergebnissen als sinnvoll erwiesen.

Summary Two Italian brothers showed identical subsequent loss of anterior pituitary function during the first decades of their life, developing panhypopituitarism. The investigations carried out indicate that in this family the etiology is hereditary in nature, being X-chromosomal recessive or autosomal recessive, with the defect located at the level of either the hypothalamus or the pituitary gland