374
injection and disappeared 24 h later. Late responses resembled flat reddish papules of 2-6 mm diameter that appeared 72-96 h after injection, reached a maximum size after 1 week, and lasted for more than 3 weeks. Titration of L 1/1/2 antigen was done in one patient and showed discernible positive reactions (late) with up to 1/100 dilution of the protein preparation (equal to O’l1 Itg fusion protein). Histopathology of early response biopsy specimens showed an Arthus-like reaction with neutrophilic vasculitis and vascular IgM and C3 deposits. Late response specimens had dense lymphocytic infiltrates that were similar to the tuberculin reactionz and to the infiltrate seen in spontaneously regressing plane warts3 (predominantly UCHL-1positive memory cells, natural killer cells virtually absent, a few scattered giant cells). None of the five controls had anti-HPV-16 E4 antibodies, whereas in four of six CIN patients, including the one with a negative skin test, seroreactivity to the E4 protein was detectable. We conclude from these preliminary data that recombinant HPV 16 proteins can elicit clinically appreciable and specific skin reactions. These reactions are directed against the virion protein Ll and not against the E4 protein. This is noteworthy since antibodies against E4 can be detected in up to 42-6% of patients with CIN.’ In-vivo tests might reproduce the complex immunoreaction to HPV more exactly than in-vitro assays. R. HÖPFL M. SANDBICHLER N. SEPP K. HEIM Departments of Dermatology E. MÜLLER-HOLZNER and Obstetrics and Gynaecology, B. WARTUSCH University of Innsbruck, A-6020 Innsbruck, Austria O. DAPUNT
German Cancer Research Centre,
I. JOCHMUS-KUDIELKA J. TER MEULEN
Heidelberg, Germany
L. GISSMANN
Department of Dermatology, University of Innsbruck
P. FRITSCH
Department of Virology,
1. Schreier AA, Allen WP, Laughlin C, Gruber J. Prospects for Human Papillomavirus Vaccines and Immunotherapies. J Natl Cancer Inst 1988; 80: 896-99. 2. Kuramoto Y, Tagami H. Histopathologic pattern analysis of human intracutaneous tuberculin reaction. Am J Dermatopathol 1989, 11: 329-37. 3. Iwatsuki K, Tagami H, Takigawa M, Yamada M. Plane warts under spontaneus regression. Arch Dermatol 1986; 122: 655-59. 4. Jochmus-Kudielka I, Schneider A, Braun R, et al. Antibodies against the human papillomavirus type 16 early proteins in human sera correlation of anti-E7 reactivity with cervical cancer. J Natl Cancer Int 1989; 81: 1698-704.
CD4 expression in
lung fibroblasts
SiR,—We have previously characterised functionally distinct
subpopulations of mouse lung fibroblasts based on the presence or absence of Thy 1 surface glycoprotein.l We have also tested for the CD4 antigen on 5 stable lines of human lung fibroblasts established in tissue culture from pneumonectomy specimens (passages 4 to 15). Fibroblasts were stained with either a monoclonal antibody against CD4 (OK-T4a-FITC or Leu-3a-PE) or an isotype control antibody with subsequent flow cytometry: Source Adult lung (cancer) Adult lung (cancer) Adult lung (cancer) Adult lung (fibrotic) Newborn lung (sepsis)
CD4
(%)
32 15 12 5 0
5% to 32% of adult lung fibroblasts displayed CD4. In contrast, newborn lung, synovial, gingival, and dermal fibroblasts did not express CD4. Indirect immunofluorescence microscopy confirmed diffuse staining for CD4 on individual cells. CD4 is a 57 kD surface glycoprotein that serves both as a high-affinity receptor for the HIV envelope glycoprotein (gp 120)2 and as a marker for subsets of T-lymphocytes. CD4 has been detected on other cell types, including monocyte-macrophages, neurons, glial cells, and glomerular mesangial cells.3 In addition, fibroblast-like cells obtained from bronchoalveolar lavage fluid may express CD4 and undergo infection by HIV.4 Our report shows that a subset of human lung interstitial fibroblasts possesses a receptor
for HIV that could serve as a stimulus for the lymphocytic alveolius associated with HIV infection. Since CD4 has affinity for class II MHC antigen, we suggest that subsets of CD4-expressing fibroblasts may be able to receive activation signals from class II MHC-bearing antigen presenting cells and contribute to the pathogenesis of idiopathic fibrosing lung diseases. We are now evaluating the expression of CD4 on interstitial lung fibroblasts obtained from patients with fibrosing lung disorders. Pulmonary/Critical Care Medicine Service, Wilford Hall USAF Medical Center, San Antonio, Texas 78236-5300, USA
STEPHEN DERDAK
Clinical Investigation Directorate, Wilford Hall USAF Medical Center
PATRICIA DIXON
University of Rochester Cancer Center, Rochester, New York
HELENA WATTS DAVID PENNEY RICHARD PHIPPS
Phipps RP, Penney DP, Keng P, et al Characterisation of two major populations of lung fibroblasts: distinguishing morphology and discordant display of Thy 1 and class II MHC Am J Respir Cell Mol Biol 1989; 1 65-74. 2. Levy JA. Human immunodeficiency viruses and the pathogenesis of AIDS. JAMA 1989; 261 2997-3006. 3. Karisson-Parra A, Dimeny E, Fellstrom B, Klareskog L. HIV receptors (CD4 antigen) in normal human glomerular cells. N Engl JMed 1989; 320 741 4. Plata F, Garcia-Pons F, Ryter A, et al. HIV-l infection of lung alveolar fibroblasts and macrophages in humans. Aids Res Hum Retroviruses 1990; 6 979-86. 1.
Unlinked anonymous testing for HIV infection SIR,-Following our survey in 1989’ we have continued unlinked anonymous testing for HIV infection in sera collected in the clinical chemistry department of East Birmingham Hospital. Pools of 10 sera were tested as previously, except that pools positive for HIV antibody by the Abbott recombinant HIV-1/HIV-2 test were confirmed by a passive agglutination test (’Serodia’) and typed by the ’LiaTek’ peptide hybridisation system (Organon Teknika). 6972 sera in 750 pools were collected between December, 1989, and December, 1990. The age and sex distribution of patients were as in the previous year, the young (1-29 years) being underrepresented 2-3 fold and those over 60 being over-represented by a factor of 2-5 when compared with the general population. Only one pool, in the 30-39-year-old male group, was HIV positive, for an annual prevalence of 1 in 6972 (95 % confidence interval 1 in 1075 to 1 in 133 300). The probability that this pool contained two positive sera was 1 in 4-9 million. During this period of anonymous testing 62 new HIV-positive individuals were identified by named testing in the West Midlands, resulting in an annual prevalence of 1 in 83 900
(population 5-2 million).
of the 1990 figures with those of 1989, when the annual prevalence at this hospital by unlinked testing was 1 in 8155 and the prevalence in West Midlands region by named testing was 1 in 153000/ shows that the prevalence in the West Midlands remains low and has not changed significantly since the previous year. Unlinked anonymous testing for HIV infection in accidentand-emergency units,z where more young people are likely to present and where the reason for attending is not positively or negatively linked with infection, has been started. Systematic collection of such prevalence data from different parts of the population will provide better estimates of the true prevalence in the general population3and will permit new trends in HIV epidemiology to be recognised early.
Comparison
Regional Virus Laboratory and Clinical Chemistry Laboratory, East Birmingham Hospital, Birmingham B9 5ST, UK
DAWN ORTON DAINA RATCLIFFE SUSAN SKIDMORE
ALAN JONES ULRICH DESSELBERGER
S, Skidmore S, Pandov H, Desselberger U Anonymous testing for HIV infection Lancet 1990; 335: 858-59. 2. Kelen GD, Fritz S, Qadgish B, et al. Unrecognized human immunodeficiency virus infection in emergency department patients. N EnglJ Med 1988, 318: 1645-50 3. Gill ON, Adler MV, Day NA Monitoring the prevalence of HIV. foundations for a programme of unlinked anonymous testing in England and Wales. Br Med J 1989, 299: 1295-98 1. Mawson
injection and disappeared 24 h later. Late responses resembled flat reddish papules of 2-6 mm diameter that appeared 72-96 h after injection, reached a maximum size after 1 week, and lasted for more than 3 weeks. Titration of L 1/1/2 antigen was done in one patient and showed discernible positive reactions (late) with up to 1/100 dilution of the protein preparation (equal to O’l1 Itg fusion protein). Histopathology of early response biopsy specimens showed an Arthus-like reaction with neutrophilic vasculitis and vascular IgM and C3 deposits. Late response specimens had dense lymphocytic infiltrates that were similar to the tuberculin reactionz and to the infiltrate seen in spontaneously regressing plane warts3 (predominantly UCHL-1positive memory cells, natural killer cells virtually absent, a few scattered giant cells). None of the five controls had anti-HPV-16 E4 antibodies, whereas in four of six CIN patients, including the one with a negative skin test, seroreactivity to the E4 protein was detectable. We conclude from these preliminary data that recombinant HPV 16 proteins can elicit clinically appreciable and specific skin reactions. These reactions are directed against the virion protein Ll and not against the E4 protein. This is noteworthy since antibodies against E4 can be detected in up to 42-6% of patients with CIN.’ In-vivo tests might reproduce the complex immunoreaction to HPV more exactly than in-vitro assays. R. HÖPFL M. SANDBICHLER N. SEPP K. HEIM Departments of Dermatology E. MÜLLER-HOLZNER and Obstetrics and Gynaecology, B. WARTUSCH University of Innsbruck, A-6020 Innsbruck, Austria O. DAPUNT
German Cancer Research Centre,
I. JOCHMUS-KUDIELKA J. TER MEULEN
Heidelberg, Germany
L. GISSMANN
Department of Dermatology, University of Innsbruck
P. FRITSCH
Department of Virology,
1. Schreier AA, Allen WP, Laughlin C, Gruber J. Prospects for Human Papillomavirus Vaccines and Immunotherapies. J Natl Cancer Inst 1988; 80: 896-99. 2. Kuramoto Y, Tagami H. Histopathologic pattern analysis of human intracutaneous tuberculin reaction. Am J Dermatopathol 1989, 11: 329-37. 3. Iwatsuki K, Tagami H, Takigawa M, Yamada M. Plane warts under spontaneus regression. Arch Dermatol 1986; 122: 655-59. 4. Jochmus-Kudielka I, Schneider A, Braun R, et al. Antibodies against the human papillomavirus type 16 early proteins in human sera correlation of anti-E7 reactivity with cervical cancer. J Natl Cancer Int 1989; 81: 1698-704.
CD4 expression in
lung fibroblasts
SiR,—We have previously characterised functionally distinct
subpopulations of mouse lung fibroblasts based on the presence or absence of Thy 1 surface glycoprotein.l We have also tested for the CD4 antigen on 5 stable lines of human lung fibroblasts established in tissue culture from pneumonectomy specimens (passages 4 to 15). Fibroblasts were stained with either a monoclonal antibody against CD4 (OK-T4a-FITC or Leu-3a-PE) or an isotype control antibody with subsequent flow cytometry: Source Adult lung (cancer) Adult lung (cancer) Adult lung (cancer) Adult lung (fibrotic) Newborn lung (sepsis)
CD4
(%)
32 15 12 5 0
5% to 32% of adult lung fibroblasts displayed CD4. In contrast, newborn lung, synovial, gingival, and dermal fibroblasts did not express CD4. Indirect immunofluorescence microscopy confirmed diffuse staining for CD4 on individual cells. CD4 is a 57 kD surface glycoprotein that serves both as a high-affinity receptor for the HIV envelope glycoprotein (gp 120)2 and as a marker for subsets of T-lymphocytes. CD4 has been detected on other cell types, including monocyte-macrophages, neurons, glial cells, and glomerular mesangial cells.3 In addition, fibroblast-like cells obtained from bronchoalveolar lavage fluid may express CD4 and undergo infection by HIV.4 Our report shows that a subset of human lung interstitial fibroblasts possesses a receptor
for HIV that could serve as a stimulus for the lymphocytic alveolius associated with HIV infection. Since CD4 has affinity for class II MHC antigen, we suggest that subsets of CD4-expressing fibroblasts may be able to receive activation signals from class II MHC-bearing antigen presenting cells and contribute to the pathogenesis of idiopathic fibrosing lung diseases. We are now evaluating the expression of CD4 on interstitial lung fibroblasts obtained from patients with fibrosing lung disorders. Pulmonary/Critical Care Medicine Service, Wilford Hall USAF Medical Center, San Antonio, Texas 78236-5300, USA
STEPHEN DERDAK
Clinical Investigation Directorate, Wilford Hall USAF Medical Center
PATRICIA DIXON
University of Rochester Cancer Center, Rochester, New York
HELENA WATTS DAVID PENNEY RICHARD PHIPPS
Phipps RP, Penney DP, Keng P, et al Characterisation of two major populations of lung fibroblasts: distinguishing morphology and discordant display of Thy 1 and class II MHC Am J Respir Cell Mol Biol 1989; 1 65-74. 2. Levy JA. Human immunodeficiency viruses and the pathogenesis of AIDS. JAMA 1989; 261 2997-3006. 3. Karisson-Parra A, Dimeny E, Fellstrom B, Klareskog L. HIV receptors (CD4 antigen) in normal human glomerular cells. N Engl JMed 1989; 320 741 4. Plata F, Garcia-Pons F, Ryter A, et al. HIV-l infection of lung alveolar fibroblasts and macrophages in humans. Aids Res Hum Retroviruses 1990; 6 979-86. 1.
Unlinked anonymous testing for HIV infection SIR,-Following our survey in 1989’ we have continued unlinked anonymous testing for HIV infection in sera collected in the clinical chemistry department of East Birmingham Hospital. Pools of 10 sera were tested as previously, except that pools positive for HIV antibody by the Abbott recombinant HIV-1/HIV-2 test were confirmed by a passive agglutination test (’Serodia’) and typed by the ’LiaTek’ peptide hybridisation system (Organon Teknika). 6972 sera in 750 pools were collected between December, 1989, and December, 1990. The age and sex distribution of patients were as in the previous year, the young (1-29 years) being underrepresented 2-3 fold and those over 60 being over-represented by a factor of 2-5 when compared with the general population. Only one pool, in the 30-39-year-old male group, was HIV positive, for an annual prevalence of 1 in 6972 (95 % confidence interval 1 in 1075 to 1 in 133 300). The probability that this pool contained two positive sera was 1 in 4-9 million. During this period of anonymous testing 62 new HIV-positive individuals were identified by named testing in the West Midlands, resulting in an annual prevalence of 1 in 83 900
(population 5-2 million).
of the 1990 figures with those of 1989, when the annual prevalence at this hospital by unlinked testing was 1 in 8155 and the prevalence in West Midlands region by named testing was 1 in 153000/ shows that the prevalence in the West Midlands remains low and has not changed significantly since the previous year. Unlinked anonymous testing for HIV infection in accidentand-emergency units,z where more young people are likely to present and where the reason for attending is not positively or negatively linked with infection, has been started. Systematic collection of such prevalence data from different parts of the population will provide better estimates of the true prevalence in the general population3and will permit new trends in HIV epidemiology to be recognised early.
Comparison
Regional Virus Laboratory and Clinical Chemistry Laboratory, East Birmingham Hospital, Birmingham B9 5ST, UK
DAWN ORTON DAINA RATCLIFFE SUSAN SKIDMORE
ALAN JONES ULRICH DESSELBERGER
S, Skidmore S, Pandov H, Desselberger U Anonymous testing for HIV infection Lancet 1990; 335: 858-59. 2. Kelen GD, Fritz S, Qadgish B, et al. Unrecognized human immunodeficiency virus infection in emergency department patients. N EnglJ Med 1988, 318: 1645-50 3. Gill ON, Adler MV, Day NA Monitoring the prevalence of HIV. foundations for a programme of unlinked anonymous testing in England and Wales. Br Med J 1989, 299: 1295-98 1. Mawson
