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889 CD45RO and CD45RA peripheral lymphocyte subsets in HIV-1+ patients
J ALLERGY CLIN IMMUNOL VOLUME 97, NUMBER 1, PART 3
889
CD45RO and C I M S R A p e r i p h e r a l l y m p h o c y t e s u b s e t s
Abstracts 891
EBV A s s o c i a t e d L e i o m y o s a r c o m a M e t a s t a s i z i n g to Bone. B Goodman MD, ME Paul MD, IC Hanson MD, HM Rosenblatt MD. SL Abramson MD, PhD, WT Shearer MD, PhD, Houston, TX Soft tissue sarcomas are exceedingly rare in the general pediatric population, occurring at a rate of approximately 8 per million. Of these, only 1 per 5 million are leiomyosarcomas. However, in HIV hffected children the incidence of leiomyoma/leiomyosarconms is considerably increased (1:500) and linked to EBV infection. The GI, GU, and respiratory tracts are the most common sites of primary presentation with melustatlc disease usually involving liver, lungs, peritoneum, pancreas & regional lymph nodes. Our patient was a 3 ye with vertical HIV infection. Routine CXR revealed a lyric lesion in the right scapula. Her past history included severe immune suppression with a CD4 count of 24 (3%), persistent otitis media and thrush, wasting, encephalupathy, and pulmonary lymphoid hyperplasia. Her EBV serology showed fn'st evidence for past infection at 18 me. Bone scan showed only right scapula involvement. CT scans showed: lytic osseous lesions in the right scapula, 2rid sternal segment below the mmmbrium, and left ilio-ala; para-aortic and retroeaval adenopathy; and a large soft tissue lesion involving the right psoas muscle and adjacent nodes with extension into the spinal canal at L3-L4. Biopsy of the scapula was consistent with a sarcoma with myogenic differentiation, i.e. immunoreactivity for muscle specific actin, lack of immunoreactivity for desmin, and the presence of actin filanaents within the tumor cells by EM. This child represents a unique presentation for an HIV associated and most likely EBV induced leiomyosarcema; namely, metastatic bone disease.
892
Effect of Exercise on Thl- and Th2-tvne cvtokine n r o d u c t i o n in H I V - 1 i n f e c t e d s u b j e c t s . J.K. Smith MD. G. Krishnaswamv MD. D. Chi PhD. R. Dykes BS. S, Reynolds BS. & S. Berk MD. Johnson City, Tennessee. In prior studies we have found that exercise upregulates the expression of Thl- & Th2-type cytokine mRNA transcripts by circulating lymphocytes of HIV-1 infected subjects. We now report the effects of exercise on Thl (IL-2, IFN~t)& Th2 (IL-4, IL-5) cytokine production by PHA-stimulated lymphocytes of HIV-I infected persons. Six HIV-I seropusitive subjects exercised on a bicycle for 30 minutes at >70% of their heart rate reserve. Blood samples were taken prior to (P) and at 0 (A0), 60 (A60), 120 (A120), 360 (A360) & 720 (A720) minutes after exercise. Lymphocytes (2 x 106/ml) were incubated for 48 hrs with (L+) & without (L-) 5 ,,g/ml PHA. Supernatants were assayed by ELISA for IL-2, 1FN-y, IL-4 & IL-5. Lymphocyte proliferation was measured by 3H incorporation. Pre- & post-exercise L+ produced IFN,t, IL-4 & IL-5 in all 6 subjects, and IL-2 in 3 & 5 subjects, respectively. The mean levels of L+ cytokines increased over P in 80% of post-exercise samples; greatest increases occurred with IL-2 (227% at A320), IFN¥ (115% at A60), IL-5 (113% at A60), & IL-4 (65% at A60). Total (Thl + Th2) L+ cytokine production increased over P at A60 (p=0.0406), A 120 (p=0.1407), A360 (p=0.0206) & A720 (p=0.0130), reaching a peak of 199% of P values at A360. Cytokine levels did not correlate with proliferation, but did correlate with cytokine transcripts measured in a prior study in the same subjects. There was no appreciable cytokine production by L-. We conclude that moderate short-term exercise enhances Th 1- and Th2-type cytokine production by PHA-stimulated lymphocytes in HIV-I infected subjects.
in H I V - l + p a t i e n t s . GS Del Giaceo MD, V Arangino MD. S Lombardini DSc. E Manta DSc. B Ambrosini DSc, [. Di Martiuo DSe. S Del Cfiacco MD. PE Maneoni MD. Cagliari, Italy In vitro experiments have suggested that HIV-1 spreading in vivo could result in preferential infection, with subsequent loss of, CD4+ T "memory" cells, as fenotypically identified with the marker CD45P.O. Such a selective loss could account for the decreased responsiveness of CD4+ T cells from HIV-1 + patients to recall antigens. In this study we have analized the expression of the antigens CD45RA and C'D45RO on peripheral blood CD4+ and CD8+ T cells from 21 IilV-I+ patients (range of peripheral CD4+ cells: 10920/~1) by FACScan triple fluorescence analysis on whole blood samples (with anti CD45RA-Fitc, anti CIM5RO-Phycoeritryn and anti CD4-PerCP). As cells from H1V-I+ patients show reduced CD4 expression and poor separation from monocyles by ligth scatter analysis, CD4+ T cells have been identified setting a logical gate to accept cells simultaneously identified both from combined scatter signals (forward and rigth) and CD4 fluorescence signals. We have found reduced percentages of CD45RA+ cells in both CD4+ and CD8+ T cell subsets in HIV-I+ patients (33.9-+19.1% of CD4+ T cells from patients versus 42.5--.11.4 % in controls, mean±SD, P=0.087, and 39.3-+19.1% of HIV-I+ CD8+ cells vs 56-+12.9 in controls, P=0.087), and increased percentages of CD45RO+ cells, especially in the CD8+ subset (P=0.0042). Our results do not support the hypotesis of selective CD45RO+ T cell loss in HIV-I+ patients; instead CD45RO+ subsets seem to be increased, possibly as a result of a persistent immunologic activation in response to HIV-1 or other infections agents.
890
Nasal E p i t h e l i a l A l t e r a t i o n s A r e A s s o c i a t e d W i t h C h r o n i c N a s a l S y m p t o m s in H I V I n f e c t i o n . E Clarin MD, M Lee MD, and RY Lin MD, New York N'Y. We have previously reported the presence of chronic nasal symptoms in adult HIV clinic patients(Ann Allergy 74:510, 1995). To explore the pathuphysiology of this phenomenon, nasal cytology was examined in 48 patients from the same urban hospital clinic using the Rhiuoprob¢ TM device. Chronic nasal symptoms(CNS) were reported by 47% of patients as defined as sneezing/stuMness/running/itching for greater than 2 weeks in duration. A history of allergic rhinitis was reported in 8% of patients. The presence of chronic nasal symptoms was signieantly associated with epithelial cell nuclear abnormalities (fisher's exact test, p=0.04). The percent of vacuolated epithelial cells was increased in patients reporting allergic rhinitis(p=0.002) and tended to be increased in patients reporting recent upper respiratory infections(URI), but was decreased in patients reporting CNS(p=0.046). These effects were independent of each other as assessed by multi.way ANOVA. The percent vacuolated epithelial cells was significantly higher in the presence of any epithelial cell degeneration(p=0.002). However, adjustment for this association did not alter the significant relationships between the percent of vacuolated epithelial cells and either CNS or allergic rhinitis+_URI. Peripheral blood CD4 counts, nasal leukocyte differential patterns, nasal goblet cell clusters, and percent goblet cells in the nasal epithelium were similar in patients with and without CNS. These data confirm that chronic nasal symptoms are prevalent in HIV infection and suggests that the pathophysiology in patients with CNS may differ from that which occurs with patients with allergic or viral rhinitis.
405
889
CD45RO and C I M S R A p e r i p h e r a l l y m p h o c y t e s u b s e t s
Abstracts 891
EBV A s s o c i a t e d L e i o m y o s a r c o m a M e t a s t a s i z i n g to Bone. B Goodman MD, ME Paul MD, IC Hanson MD, HM Rosenblatt MD. SL Abramson MD, PhD, WT Shearer MD, PhD, Houston, TX Soft tissue sarcomas are exceedingly rare in the general pediatric population, occurring at a rate of approximately 8 per million. Of these, only 1 per 5 million are leiomyosarcomas. However, in HIV hffected children the incidence of leiomyoma/leiomyosarconms is considerably increased (1:500) and linked to EBV infection. The GI, GU, and respiratory tracts are the most common sites of primary presentation with melustatlc disease usually involving liver, lungs, peritoneum, pancreas & regional lymph nodes. Our patient was a 3 ye with vertical HIV infection. Routine CXR revealed a lyric lesion in the right scapula. Her past history included severe immune suppression with a CD4 count of 24 (3%), persistent otitis media and thrush, wasting, encephalupathy, and pulmonary lymphoid hyperplasia. Her EBV serology showed fn'st evidence for past infection at 18 me. Bone scan showed only right scapula involvement. CT scans showed: lytic osseous lesions in the right scapula, 2rid sternal segment below the mmmbrium, and left ilio-ala; para-aortic and retroeaval adenopathy; and a large soft tissue lesion involving the right psoas muscle and adjacent nodes with extension into the spinal canal at L3-L4. Biopsy of the scapula was consistent with a sarcoma with myogenic differentiation, i.e. immunoreactivity for muscle specific actin, lack of immunoreactivity for desmin, and the presence of actin filanaents within the tumor cells by EM. This child represents a unique presentation for an HIV associated and most likely EBV induced leiomyosarcema; namely, metastatic bone disease.
892
Effect of Exercise on Thl- and Th2-tvne cvtokine n r o d u c t i o n in H I V - 1 i n f e c t e d s u b j e c t s . J.K. Smith MD. G. Krishnaswamv MD. D. Chi PhD. R. Dykes BS. S, Reynolds BS. & S. Berk MD. Johnson City, Tennessee. In prior studies we have found that exercise upregulates the expression of Thl- & Th2-type cytokine mRNA transcripts by circulating lymphocytes of HIV-1 infected subjects. We now report the effects of exercise on Thl (IL-2, IFN~t)& Th2 (IL-4, IL-5) cytokine production by PHA-stimulated lymphocytes of HIV-I infected persons. Six HIV-I seropusitive subjects exercised on a bicycle for 30 minutes at >70% of their heart rate reserve. Blood samples were taken prior to (P) and at 0 (A0), 60 (A60), 120 (A120), 360 (A360) & 720 (A720) minutes after exercise. Lymphocytes (2 x 106/ml) were incubated for 48 hrs with (L+) & without (L-) 5 ,,g/ml PHA. Supernatants were assayed by ELISA for IL-2, 1FN-y, IL-4 & IL-5. Lymphocyte proliferation was measured by 3H incorporation. Pre- & post-exercise L+ produced IFN,t, IL-4 & IL-5 in all 6 subjects, and IL-2 in 3 & 5 subjects, respectively. The mean levels of L+ cytokines increased over P in 80% of post-exercise samples; greatest increases occurred with IL-2 (227% at A320), IFN¥ (115% at A60), IL-5 (113% at A60), & IL-4 (65% at A60). Total (Thl + Th2) L+ cytokine production increased over P at A60 (p=0.0406), A 120 (p=0.1407), A360 (p=0.0206) & A720 (p=0.0130), reaching a peak of 199% of P values at A360. Cytokine levels did not correlate with proliferation, but did correlate with cytokine transcripts measured in a prior study in the same subjects. There was no appreciable cytokine production by L-. We conclude that moderate short-term exercise enhances Th 1- and Th2-type cytokine production by PHA-stimulated lymphocytes in HIV-I infected subjects.
in H I V - l + p a t i e n t s . GS Del Giaceo MD, V Arangino MD. S Lombardini DSc. E Manta DSc. B Ambrosini DSc, [. Di Martiuo DSe. S Del Cfiacco MD. PE Maneoni MD. Cagliari, Italy In vitro experiments have suggested that HIV-1 spreading in vivo could result in preferential infection, with subsequent loss of, CD4+ T "memory" cells, as fenotypically identified with the marker CD45P.O. Such a selective loss could account for the decreased responsiveness of CD4+ T cells from HIV-1 + patients to recall antigens. In this study we have analized the expression of the antigens CD45RA and C'D45RO on peripheral blood CD4+ and CD8+ T cells from 21 IilV-I+ patients (range of peripheral CD4+ cells: 10920/~1) by FACScan triple fluorescence analysis on whole blood samples (with anti CD45RA-Fitc, anti CIM5RO-Phycoeritryn and anti CD4-PerCP). As cells from H1V-I+ patients show reduced CD4 expression and poor separation from monocyles by ligth scatter analysis, CD4+ T cells have been identified setting a logical gate to accept cells simultaneously identified both from combined scatter signals (forward and rigth) and CD4 fluorescence signals. We have found reduced percentages of CD45RA+ cells in both CD4+ and CD8+ T cell subsets in HIV-I+ patients (33.9-+19.1% of CD4+ T cells from patients versus 42.5--.11.4 % in controls, mean±SD, P=0.087, and 39.3-+19.1% of HIV-I+ CD8+ cells vs 56-+12.9 in controls, P=0.087), and increased percentages of CD45RO+ cells, especially in the CD8+ subset (P=0.0042). Our results do not support the hypotesis of selective CD45RO+ T cell loss in HIV-I+ patients; instead CD45RO+ subsets seem to be increased, possibly as a result of a persistent immunologic activation in response to HIV-1 or other infections agents.
890
Nasal E p i t h e l i a l A l t e r a t i o n s A r e A s s o c i a t e d W i t h C h r o n i c N a s a l S y m p t o m s in H I V I n f e c t i o n . E Clarin MD, M Lee MD, and RY Lin MD, New York N'Y. We have previously reported the presence of chronic nasal symptoms in adult HIV clinic patients(Ann Allergy 74:510, 1995). To explore the pathuphysiology of this phenomenon, nasal cytology was examined in 48 patients from the same urban hospital clinic using the Rhiuoprob¢ TM device. Chronic nasal symptoms(CNS) were reported by 47% of patients as defined as sneezing/stuMness/running/itching for greater than 2 weeks in duration. A history of allergic rhinitis was reported in 8% of patients. The presence of chronic nasal symptoms was signieantly associated with epithelial cell nuclear abnormalities (fisher's exact test, p=0.04). The percent of vacuolated epithelial cells was increased in patients reporting allergic rhinitis(p=0.002) and tended to be increased in patients reporting recent upper respiratory infections(URI), but was decreased in patients reporting CNS(p=0.046). These effects were independent of each other as assessed by multi.way ANOVA. The percent vacuolated epithelial cells was significantly higher in the presence of any epithelial cell degeneration(p=0.002). However, adjustment for this association did not alter the significant relationships between the percent of vacuolated epithelial cells and either CNS or allergic rhinitis+_URI. Peripheral blood CD4 counts, nasal leukocyte differential patterns, nasal goblet cell clusters, and percent goblet cells in the nasal epithelium were similar in patients with and without CNS. These data confirm that chronic nasal symptoms are prevalent in HIV infection and suggests that the pathophysiology in patients with CNS may differ from that which occurs with patients with allergic or viral rhinitis.
405