IL-12 reverses cytokine and immune abnormalities in Sezary syndrome

A. H. Rook, M. Kubin, M. Cassin, E. C. Vonderheid, B. R. Vowels, J. T. Wolfe, S. F. Wolf, A. Singh, G. Trinchieri, S. R. Lessin

Research output: Contribution to journalArticle

Abstract

Cutaneous T cell lymphoma is a lymphoproliferative disorder typically characterized by skin invasion of clonally derived malignant CD4+ lymphocytes that phenotypically resemble mature Th cells. Sezary syndrome (SzS) represents an advanced form of cutaneous T cell lymphoma associated with generalized erythroderma and involvement of the peripheral blood by the malignant cell population. We have previously demonstrated aberrant cytokine production by PBMC in SzS characterized by increased IL-4 and deficient IL-2 and IFN-γ production, as well as increased expression of mRNA for IL-4 and IL-5 within active skin lesions, suggesting that the clonal T cell population is derived from the Th 2 subset of helper T lymphocytes. These findings have been associated with a constellation of immune abnormalities that have been attributed to the cytokine abnormalities. Because IL-12 is a potent inducer of IFN-γ production, and causes the activation of cytotoxic lymphocytes, we examined the production of IL-12 by PBMC from SzS patients and whether IL-12 could alter the unfavorable cytokine balance typical of SzS and thus lead to correction of immune defects. Despite normal numbers of peripheral blood monocytes and normal TNF-α production, mean Staphyloccus aureus and LPS- induced IL-12 p40 and p70 production by SzS PBMC was significantly decreased compared with PBMC from normal controls. Mean IFN-γ production by patient PBMC in response to PHA alone was depressed, but increased to levels comparable with normal after addition of 1 ng/ml IL-12. Pretreatment of PBMC for 24 h with IL-12, IFN-α, or both together resulted in a decrease in PHA- stimulated IL-4 production from a base line of 1818 pg/ml to 1520, 1350, and 1058 pg/ml, respectively. Lastly, culture of patient PBMC with IL-12 for 24 h also resulted in significant increases in NK activity against K562 cells. These results indicate that PBMC from patients with SzS manifest a defect in IL-12 production and that the cytokine abnormalities associated with SzS can be favorably altered by IL-12.

Original languageEnglish (US)
Pages (from-to)1491-1498
Number of pages8
JournalJournal of Immunology
Volume154
Issue number3
StatePublished - 1995
Externally publishedYes

Fingerprint

Sezary Syndrome
Interleukin-12
Cytokines
Interleukin-4
Cutaneous T-Cell Lymphoma
Exfoliative Dermatitis
Skin
Lymphoproliferative Disorders
K562 Cells
Interleukin-5
Lymphocyte Activation
Helper-Inducer T-Lymphocytes
Population
Interleukin-2
Monocytes
Blood Cells
Lymphocytes
T-Lymphocytes

ASJC Scopus subject areas

  • Immunology

Cite this

Rook, A. H., Kubin, M., Cassin, M., Vonderheid, E. C., Vowels, B. R., Wolfe, J. T., ... Lessin, S. R. (1995). IL-12 reverses cytokine and immune abnormalities in Sezary syndrome. Journal of Immunology, 154(3), 1491-1498.

IL-12 reverses cytokine and immune abnormalities in Sezary syndrome. / Rook, A. H.; Kubin, M.; Cassin, M.; Vonderheid, E. C.; Vowels, B. R.; Wolfe, J. T.; Wolf, S. F.; Singh, A.; Trinchieri, G.; Lessin, S. R.

In: Journal of Immunology, Vol. 154, No. 3, 1995, p. 1491-1498.

Research output: Contribution to journalArticle

Rook, AH, Kubin, M, Cassin, M, Vonderheid, EC, Vowels, BR, Wolfe, JT, Wolf, SF, Singh, A, Trinchieri, G & Lessin, SR 1995, 'IL-12 reverses cytokine and immune abnormalities in Sezary syndrome', Journal of Immunology, vol. 154, no. 3, pp. 1491-1498.
Rook AH, Kubin M, Cassin M, Vonderheid EC, Vowels BR, Wolfe JT et al. IL-12 reverses cytokine and immune abnormalities in Sezary syndrome. Journal of Immunology. 1995;154(3):1491-1498.
Rook, A. H. ; Kubin, M. ; Cassin, M. ; Vonderheid, E. C. ; Vowels, B. R. ; Wolfe, J. T. ; Wolf, S. F. ; Singh, A. ; Trinchieri, G. ; Lessin, S. R. / IL-12 reverses cytokine and immune abnormalities in Sezary syndrome. In: Journal of Immunology. 1995 ; Vol. 154, No. 3. pp. 1491-1498.
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abstract = "Cutaneous T cell lymphoma is a lymphoproliferative disorder typically characterized by skin invasion of clonally derived malignant CD4+ lymphocytes that phenotypically resemble mature Th cells. Sezary syndrome (SzS) represents an advanced form of cutaneous T cell lymphoma associated with generalized erythroderma and involvement of the peripheral blood by the malignant cell population. We have previously demonstrated aberrant cytokine production by PBMC in SzS characterized by increased IL-4 and deficient IL-2 and IFN-γ production, as well as increased expression of mRNA for IL-4 and IL-5 within active skin lesions, suggesting that the clonal T cell population is derived from the Th 2 subset of helper T lymphocytes. These findings have been associated with a constellation of immune abnormalities that have been attributed to the cytokine abnormalities. Because IL-12 is a potent inducer of IFN-γ production, and causes the activation of cytotoxic lymphocytes, we examined the production of IL-12 by PBMC from SzS patients and whether IL-12 could alter the unfavorable cytokine balance typical of SzS and thus lead to correction of immune defects. Despite normal numbers of peripheral blood monocytes and normal TNF-α production, mean Staphyloccus aureus and LPS- induced IL-12 p40 and p70 production by SzS PBMC was significantly decreased compared with PBMC from normal controls. Mean IFN-γ production by patient PBMC in response to PHA alone was depressed, but increased to levels comparable with normal after addition of 1 ng/ml IL-12. Pretreatment of PBMC for 24 h with IL-12, IFN-α, or both together resulted in a decrease in PHA- stimulated IL-4 production from a base line of 1818 pg/ml to 1520, 1350, and 1058 pg/ml, respectively. Lastly, culture of patient PBMC with IL-12 for 24 h also resulted in significant increases in NK activity against K562 cells. These results indicate that PBMC from patients with SzS manifest a defect in IL-12 production and that the cytokine abnormalities associated with SzS can be favorably altered by IL-12.",
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T1 - IL-12 reverses cytokine and immune abnormalities in Sezary syndrome

AU - Rook, A. H.

AU - Kubin, M.

AU - Cassin, M.

AU - Vonderheid, E. C.

AU - Vowels, B. R.

AU - Wolfe, J. T.

AU - Wolf, S. F.

AU - Singh, A.

AU - Trinchieri, G.

AU - Lessin, S. R.

PY - 1995

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N2 - Cutaneous T cell lymphoma is a lymphoproliferative disorder typically characterized by skin invasion of clonally derived malignant CD4+ lymphocytes that phenotypically resemble mature Th cells. Sezary syndrome (SzS) represents an advanced form of cutaneous T cell lymphoma associated with generalized erythroderma and involvement of the peripheral blood by the malignant cell population. We have previously demonstrated aberrant cytokine production by PBMC in SzS characterized by increased IL-4 and deficient IL-2 and IFN-γ production, as well as increased expression of mRNA for IL-4 and IL-5 within active skin lesions, suggesting that the clonal T cell population is derived from the Th 2 subset of helper T lymphocytes. These findings have been associated with a constellation of immune abnormalities that have been attributed to the cytokine abnormalities. Because IL-12 is a potent inducer of IFN-γ production, and causes the activation of cytotoxic lymphocytes, we examined the production of IL-12 by PBMC from SzS patients and whether IL-12 could alter the unfavorable cytokine balance typical of SzS and thus lead to correction of immune defects. Despite normal numbers of peripheral blood monocytes and normal TNF-α production, mean Staphyloccus aureus and LPS- induced IL-12 p40 and p70 production by SzS PBMC was significantly decreased compared with PBMC from normal controls. Mean IFN-γ production by patient PBMC in response to PHA alone was depressed, but increased to levels comparable with normal after addition of 1 ng/ml IL-12. Pretreatment of PBMC for 24 h with IL-12, IFN-α, or both together resulted in a decrease in PHA- stimulated IL-4 production from a base line of 1818 pg/ml to 1520, 1350, and 1058 pg/ml, respectively. Lastly, culture of patient PBMC with IL-12 for 24 h also resulted in significant increases in NK activity against K562 cells. These results indicate that PBMC from patients with SzS manifest a defect in IL-12 production and that the cytokine abnormalities associated with SzS can be favorably altered by IL-12.

AB - Cutaneous T cell lymphoma is a lymphoproliferative disorder typically characterized by skin invasion of clonally derived malignant CD4+ lymphocytes that phenotypically resemble mature Th cells. Sezary syndrome (SzS) represents an advanced form of cutaneous T cell lymphoma associated with generalized erythroderma and involvement of the peripheral blood by the malignant cell population. We have previously demonstrated aberrant cytokine production by PBMC in SzS characterized by increased IL-4 and deficient IL-2 and IFN-γ production, as well as increased expression of mRNA for IL-4 and IL-5 within active skin lesions, suggesting that the clonal T cell population is derived from the Th 2 subset of helper T lymphocytes. These findings have been associated with a constellation of immune abnormalities that have been attributed to the cytokine abnormalities. Because IL-12 is a potent inducer of IFN-γ production, and causes the activation of cytotoxic lymphocytes, we examined the production of IL-12 by PBMC from SzS patients and whether IL-12 could alter the unfavorable cytokine balance typical of SzS and thus lead to correction of immune defects. Despite normal numbers of peripheral blood monocytes and normal TNF-α production, mean Staphyloccus aureus and LPS- induced IL-12 p40 and p70 production by SzS PBMC was significantly decreased compared with PBMC from normal controls. Mean IFN-γ production by patient PBMC in response to PHA alone was depressed, but increased to levels comparable with normal after addition of 1 ng/ml IL-12. Pretreatment of PBMC for 24 h with IL-12, IFN-α, or both together resulted in a decrease in PHA- stimulated IL-4 production from a base line of 1818 pg/ml to 1520, 1350, and 1058 pg/ml, respectively. Lastly, culture of patient PBMC with IL-12 for 24 h also resulted in significant increases in NK activity against K562 cells. These results indicate that PBMC from patients with SzS manifest a defect in IL-12 production and that the cytokine abnormalities associated with SzS can be favorably altered by IL-12.

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