characterization of the suppressive properties of human cd4+cd25+ t cells in atopic and non-atopic...

1
397 Clinical Status, Serum Immunoglobulin G Subclasses and Sputum Il-10 and Mpo Levels in Cf Patients A. Korzeniewska, J. Jerzynska, I. Stelmach; Department of Pediatrics and Allergy, Medical University of Lodz, M Curie Hospital, Zgierz, POLAND. RATIONALE: This study was undertaken to define a correlation between clinical status, serum immunoglobuline G (IgG) subclasses and sputum IL-10 and MPO levels in patients with CF. METHODS: We examined 17 clinical stable CF patients aged 12-30. All patients were chronic infected with Pseudomonas aeruginosa. Shwach- man-Kulczycki Score (SKS) was measured. Total IgG, IgG1, IgG2, IgG3, IgG4 (mg/dl) in serum and sputum IL-10 (pg/dl) and MPO (ng/dl) levels were determined. RESULTS: Mean SKS was 76±13. Mean total IgG levels were 1510±556.9, IgG1 9.552±2.5l, IgG2 4.8±2.04, IgG3 1.058±0.6 and IgG4 1.787±0.725. Mean sputum IL-10 levels were 10.78±0.76 and MPO levels 5.01±0.53. We found significant correlation between elevated total serum IgG levels and decreased SKS (p=0.002). High levels of IgG2 were significantly cor- related with decreased SKS (p=0.001). Significant correlation between IgG2 and sputum MPO (p=0.002) levels was observed; and there was sig- nificant inverse correlation between IgG2 levels and sputum IL-10 (p=0.001) levels. There was significant correlation between elevated lev- els of IgG4 and increased SKS (p=0.002) and IL-10 levels (p=0.003). Sig- nificant inverse correlation between IgG4 levels and sputum (p=0.001) MPO levels were observed. We found significant correlation between better SKS and IL-10 levels (p=0.002) and significant inverse correlation between SKS and sputum MPO levels (p=0.002). CONCLUSIONS: IgG2 levels showed to be a good value in predicting the severity of disease and could be a useful marker of inflammatory process in CF patients chronic infected with Pseudomonas aeruginosa. Elevated levels of IgG4 may antagonise IgG2 helping to preserve rela- tively good clinical status. 398 Evaluation of NK T Cells in Patients with Schistosomiasis and Asthma R. A. Campos, M. S. Teles, M. J. Martins, O. F. Jesus, B. B. Andrade, A. A. Cruz, M. Araújo, E. M. Carvalho; Internal Medicine, Universidade Federal da Bahia, Salvador-BA, BRAZIL. RATIONALE: S. mansoni modulates the immune response in asthma. V24V11 NK T cells release Th1 and Th2 cytokines but there is a pos- itive correlation between CD4 expression on NKT cells and ability to pro- duce Th2 cytokines. NKT cell deficient mice infected with S. mansoni present reduced hepatic pathology. This study evaluated the profile of NK T cells in asthmatic patients with schistosomiasis. METHODS: We evaluated 4 groups: 1) controls; 2) asthma; 3) schisto- somiasis; 4) asthma + schistosomiasis. A questionnaire for asthma was done and FACS analysis of the PBMC for NKT cells and intracellular cytokines using PE and FITC anti-V24, FITC anti-V11, Cy anti-CD4, Cy anti-CD3, PE anti-IL-4 and PE anti-IFN-. NK T cells were defined by the double expression of V24 and V11. RESULTS: We evaluated 87 subjects: 25 from group 1, 39 from group 2, 12 from group 3 and 11 from group 4. There was a reduction on NKT cells in asthma (group 1: 0.45%±0.41 and group 2: 0.14%±0.21; p=0.03) but CD4 + NKT cells were higher (group 1: 35%±4.1; group 2: 57%±5.6). There was no reduction of NKT cells in schistosomiasis and in the asthmatic indi- viduals with schistosomiasis. The NKT cell intracellular production of IL-4 was similar between groups 3 and 4. Subjects with schistosomiasis and asthma showed a non significant lower INF- production. CONCLUSIONS: In asthma, CD4 + V24V11 NKT may be preferen- tially producing Th2 cytokines and this may be modulated in schistoso- miasis patients likely by stimulating CD4 - V24V11 NKT to produce Th1 cytokines. Funding: FAPESB 399 Successful Treatment Using Interleukin-2 (IL-2) in a Patient with Idiopathic CD4+ Lymphopenia (ICL) and Mycobacterium avium (M.avium) B. Mandal 1 , V. Bhushan 2 , D. Khan 1 ; 1 Allergy and Immunology, UT Southwestern, Dallas, TX, 2 Hematology/Oncology, UT Southwestern, Dallas, TX. RATIONALE: ICL is a rare immune defect characterized by: CD4 + T cells count <300 cells/mm 3 on more than one occasion, lack of HIV infec- tion or other immune deficiency, and presence of opportunistic infections. Isolated case reports suggest that IL-2 is efficacious in ICL. We report a case of a patient with M.avium due to ICL who was successfully treated with IL-2. METHODS: This patient is a 39 y/o WM who presented with 2 years of chronic cough and dyspnea. A sputum culture revealed M.avium. His CD4 + T cells were decreased at 182 cells/l. Workup for other etiologies of CD4 + lymphopenia was negative including: HIV-1,2 , HTLV-1,2, chest CT and bone marrow biopsy. He was diagnosed with ICL and started on pegylated subcutaneous IL-2 at 500,000 units weekly. He was given incrementally higher doses until he reached a maintenance dosage 3 months later of 11 MU weekly. RESULTS: After 3 months of therapy, CD4 + T cells increased to 453 cells/l. Nine months after initiation of IL-2, his CD4 + T cell counts have been >450 cells/l. Sputum cultures became negative for M.avium, and he has tolerated the IL-2 with no side effects. CONCLUSIONS: IL-2 therapy appears to be a relatively safe and effec- tive treatment for patients with ICL and should be considered for select patients to prevent the high morbidity associated with this syndrome. Funding: UT Southwestern 400 Characterization of the Suppressive Properties of Human CD4+CD25+ T Cells in Atopic and Non-Atopic Individuals A. M. L. Fonseca, C. Torres, O. M. M. Lourenco, L. M. P. Taborda-Barata; Department of Medical Sciences, Health Sciences Medical Center, Uni- versity of Beira interior, Covilhã, PORTUGAL. RATIONALE: The aim of the present study was to analyze whether “regulatory” CD4+CD25+ T cells are present and function normally in atopic individuals, namely in terms of the suppression of allergen-specific proliferation and cytokine production of CD4+CD25 T cells. METHODS: Peripheral blood was obtained from 12 atopic subjects and 12 non-atopic controls and CD4+CD25+ and CD4+CD25 cells were isolated using magnetic beads. CD4+CD25+ and CD4+CD25 T cells were mixed at different ratios (2: 1, 4: 1 and 8: 1) and stimulated with Der p or PHA in 6-day co-cultures together with autologous monocytes as antigen-presenting cells. Proliferation and cytokine production was analysed using thymidine incorporation and cytometric bead array, respectively. RESULTS: Our results show that the percentage of CD4+CD25+ T cells was not significantly different between groups. CD4+CD25+ cells sup- pressed proliferation by their Der p-stimulated CD4+CD25 T cells in all studied samples. Moreover, the amount of IFN-, IL-2, IL-4, IL-5, Il-10, TNF- produced by the co-cultures was comparable in both groups studied. CONCLUSIONS: These preliminary data indicate that “regulatory” CD4+CD25+ T cells are equally present and functional in both atopic and non-atopic individuals. Funding: Fundacao para a Ciencia e Tecnologia S102 Abstracts J ALLERGY CLIN IMMUNOL FEBRUARY 2006 SUNDAY

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Page 1: Characterization of the Suppressive Properties of Human CD4+CD25+ T Cells in Atopic and Non-Atopic Individuals

397 Clinical Status, Serum Immunoglobulin G Subclasses andSputum Il-10 and Mpo Levels in Cf Patients

A. Korzeniewska, J. Jerzynska, I. Stelmach; Department of Pediatrics

and Allergy, Medical University of Lodz, M Curie Hospital, Zgierz,

POLAND.

RATIONALE: This study was undertaken to define a correlation

between clinical status, serum immunoglobuline G (IgG) subclasses and

sputum IL-10 and MPO levels in patients with CF.

METHODS: We examined 17 clinical stable CF patients aged 12-30. All

patients were chronic infected with Pseudomonas aeruginosa. Shwach-

man-Kulczycki Score (SKS) was measured. Total IgG, IgG1, IgG2, IgG3,

IgG4 (mg/dl) in serum and sputum IL-10 (pg/dl) and MPO (ng/dl) levels

were determined.

RESULTS: Mean SKS was 76±13. Mean total IgG levels were

1510±556.9, IgG1 9.552±2.5l, IgG2 4.8±2.04, IgG3 1.058±0.6 and IgG4

1.787±0.725. Mean sputum IL-10 levels were 10.78±0.76 and MPO

levels 5.01±0.53.

We found significant correlation between elevated total serum IgG levels

and decreased SKS (p=0.002). High levels of IgG2 were significantly cor-

related with decreased SKS (p=0.001). Significant correlation between

IgG2 and sputum MPO (p=0.002) levels was observed; and there was sig-

nificant inverse correlation between IgG2 levels and sputum IL-10

(p=0.001) levels. There was significant correlation between elevated lev-

els of IgG4 and increased SKS (p=0.002) and IL-10 levels (p=0.003). Sig-

nificant inverse correlation between IgG4 levels and sputum (p=0.001)

MPO levels were observed. We found significant correlation between

better SKS and IL-10 levels (p=0.002) and significant inverse correlation

between SKS and sputum MPO levels (p=0.002).

CONCLUSIONS: IgG2 levels showed to be a good value in predicting

the severity of disease and could be a useful marker of inflammatory

process in CF patients chronic infected with Pseudomonas aeruginosa.

Elevated levels of IgG4 may antagonise IgG2 helping to preserve rela-

tively good clinical status.

398 Evaluation of NK T Cells in Patients with Schistosomiasis andAsthma

R. A. Campos, M. S. Teles, M. J. Martins, O. F. Jesus, B. B. Andrade, A.

A. Cruz, M. Araújo, E. M. Carvalho; Internal Medicine, Universidade

Federal da Bahia, Salvador-BA, BRAZIL.

RATIONALE: S. mansoni modulates the immune response in asthma.

V�24V�11 NK T cells release Th1 and Th2 cytokines but there is a pos-

itive correlation between CD4 expression on NKT cells and ability to pro-

duce Th2 cytokines. NKT cell deficient mice infected with S. mansonipresent reduced hepatic pathology. This study evaluated the profile of NK

T cells in asthmatic patients with schistosomiasis.

METHODS: We evaluated 4 groups: 1) controls; 2) asthma; 3) schisto-

somiasis; 4) asthma + schistosomiasis. A questionnaire for asthma was

done and FACS analysis of the PBMC for NKT cells and intracellular

cytokines using PE and FITC anti-V�24, FITC anti-V�11, Cy anti-CD4,

Cy anti-CD3, PE anti-IL-4 and PE anti-IFN-�. NK T cells were defined

by the double expression of V�24 and V�11.

RESULTS: We evaluated 87 subjects: 25 from group 1, 39 from group 2,

12 from group 3 and 11 from group 4. There was a reduction on NKT cells

in asthma (group 1: 0.45%±0.41 and group 2: 0.14%±0.21; p=0.03) but

CD4+NKT cells were higher (group 1: 35%±4.1; group 2: 57%±5.6). There

was no reduction of NKT cells in schistosomiasis and in the asthmatic indi-

viduals with schistosomiasis. The NKT cell intracellular production of IL-4

was similar between groups 3 and 4. Subjects with schistosomiasis and

asthma showed a non significant lower INF-� production.

CONCLUSIONS: In asthma, CD4+ V�24V�11 NKT may be preferen-

tially producing Th2 cytokines and this may be modulated in schistoso-

miasis patients likely by stimulating CD4 - V�24V�11 NKT to produce

Th1 cytokines.

Funding: FAPESB

399 Successful Treatment Using Interleukin-2 (IL-2) in a Patientwith Idiopathic CD4+ Lymphopenia (ICL) and Mycobacteriumavium (M.avium)

B. Mandal1, V. Bhushan2, D. Khan1; 1Allergy and Immunology, UT

Southwestern, Dallas, TX, 2Hematology/Oncology, UT Southwestern,

Dallas, TX.

RATIONALE: ICL is a rare immune defect characterized by: CD4+ T

cells count <300 cells/mm3 on more than one occasion, lack of HIV infec-

tion or other immune deficiency, and presence of opportunistic infections.

Isolated case reports suggest that IL-2 is efficacious in ICL. We report a

case of a patient with M.avium due to ICL who was successfully treated

with IL-2.

METHODS: This patient is a 39 y/o WM who presented with 2 years of

chronic cough and dyspnea. A sputum culture revealed M.avium. His

CD4+ T cells were decreased at 182 cells/�l. Workup for other etiologies

of CD4+ lymphopenia was negative including: HIV-1,2 , HTLV-1,2, chest

CT and bone marrow biopsy. He was diagnosed with ICL and started on

pegylated subcutaneous IL-2 at 500,000 units weekly. He was given

incrementally higher doses until he reached a maintenance dosage 3

months later of 11 MU weekly.

RESULTS: After 3 months of therapy, CD4+ T cells increased to 453

cells/�l. Nine months after initiation of IL-2, his CD4+ T cell counts have

been >450 cells/�l. Sputum cultures became negative for M.avium, and he

has tolerated the IL-2 with no side effects.

CONCLUSIONS: IL-2 therapy appears to be a relatively safe and effec-

tive treatment for patients with ICL and should be considered for select

patients to prevent the high morbidity associated with this syndrome.

Funding: UT Southwestern

400 Characterization of the Suppressive Properties of HumanCD4+CD25+ T Cells in Atopic and Non-Atopic Individuals

A. M. L. Fonseca, C. Torres, O. M. M. Lourenco, L. M. P. Taborda-Barata;

Department of Medical Sciences, Health Sciences Medical Center, Uni-

versity of Beira interior, Covilhã, PORTUGAL.

RATIONALE: The aim of the present study was to analyze whether

“regulatory” CD4+CD25+ T cells are present and function normally in

atopic individuals, namely in terms of the suppression of allergen-specific

proliferation and cytokine production of CD4+CD25 T cells.

METHODS: Peripheral blood was obtained from 12 atopic subjects and

12 non-atopic controls and CD4+CD25+ and CD4+CD25 cells were

isolated using magnetic beads. CD4+CD25+ and CD4+CD25 T cells

were mixed at different ratios (2: 1, 4: 1 and 8: 1) and stimulated with Der

p or PHA in 6-day co-cultures together with autologous monocytes as

antigen-presenting cells. Proliferation and cytokine production was

analysed using thymidine incorporation and cytometric bead array,

respectively.

RESULTS: Our results show that the percentage of CD4+CD25+ T cells

was not significantly different between groups. CD4+CD25+ cells sup-

pressed proliferation by their Der p-stimulated CD4+CD25 T cells in all

studied samples. Moreover, the amount of IFN-�, IL-2, IL-4, IL-5, Il-10,

TNF-� produced by the co-cultures was comparable in both groups

studied.

CONCLUSIONS: These preliminary data indicate that “regulatory”

CD4+CD25+ T cells are equally present and functional in both atopic and

non-atopic individuals.

Funding: Fundacao para a Ciencia e Tecnologia

S102 Abstracts J ALLERGY CLIN IMMUNOL

FEBRUARY 2006

SU

ND

AY