Interleukin-7 activates human naive CD4+ cells and primes for interleukin-4 production.
Interleukin (IL)-4 is considered to be essential for T helper (Th)2 cell development, yet in areas of primary T cell activation, CD4+ cells are its only source. This implies that other signals must drive the initial expression of IL-4 production. The role of CD28 co-stimulation in Th2 subset develop...
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| Format: | Journal article |
| Language: | English |
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1997
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| _version_ | 1826263204520525824 |
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| author | Webb, L Foxwell, B Feldmann, M |
| author_facet | Webb, L Foxwell, B Feldmann, M |
| author_sort | Webb, L |
| collection | OXFORD |
| description | Interleukin (IL)-4 is considered to be essential for T helper (Th)2 cell development, yet in areas of primary T cell activation, CD4+ cells are its only source. This implies that other signals must drive the initial expression of IL-4 production. The role of CD28 co-stimulation in Th2 subset development has been described. However, in mice deficient for CD28, Th2 responses are diminished, but not abrogated. Cytokines produced within the lymphoid tissue, e.g. IL-7, may be important in the primary activation of naive CD4+ cells. We have found that human naive CD4+ cells purified from umbilical cord blood express the IL-7 receptor and respond vigorously to IL-7 during primary stimulation. Naive CD4+ cells grown in IL-4, in the presence or absence of IL-2, fail to produce Th2 cytokines upon restimulation. In contrast, IL-7 induces development of a population of T cells that produce large amounts of IL-4. Growth in IL-7 also increases IL-2-induced production of interferon (IFN)-gamma and IL-10 production. IL-7-induced IL-4 production is not inhibited by neutralizing antibodies to IL-4 on its receptor. This implies that IL-7 acts directly to induce Th2 subset development and not by up-regulating either production of IL-4 during culture or expression of the IL-4 receptor. Moreover, IL-7 potentiates the effects of CD28 co-stimulation on both naive CD4+ cell proliferation and subsequent IL-4 production. Following primary stimulation, CD4+ cells lose expression of the IL-7 receptor, resulting in IL-7 unresponsiveness. This work reveals a novel role for IL-7 in the primary activation of CD4+ cells. We propose that in conjunction with CD28 co-stimulation, IL-7 induces the initial expression of IL-4 production and that IL-4 acts subsequently to expand Th2 cytokine-producing cells at the appropriate anatomical site. |
| first_indexed | 2024-03-06T19:48:01Z |
| format | Journal article |
| id | oxford-uuid:230015f7-f606-4d58-b1d1-898421c7b909 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:48:01Z |
| publishDate | 1997 |
| record_format | dspace |
| spelling | oxford-uuid:230015f7-f606-4d58-b1d1-898421c7b9092022-03-26T11:41:49ZInterleukin-7 activates human naive CD4+ cells and primes for interleukin-4 production.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:230015f7-f606-4d58-b1d1-898421c7b909EnglishSymplectic Elements at Oxford1997Webb, LFoxwell, BFeldmann, MInterleukin (IL)-4 is considered to be essential for T helper (Th)2 cell development, yet in areas of primary T cell activation, CD4+ cells are its only source. This implies that other signals must drive the initial expression of IL-4 production. The role of CD28 co-stimulation in Th2 subset development has been described. However, in mice deficient for CD28, Th2 responses are diminished, but not abrogated. Cytokines produced within the lymphoid tissue, e.g. IL-7, may be important in the primary activation of naive CD4+ cells. We have found that human naive CD4+ cells purified from umbilical cord blood express the IL-7 receptor and respond vigorously to IL-7 during primary stimulation. Naive CD4+ cells grown in IL-4, in the presence or absence of IL-2, fail to produce Th2 cytokines upon restimulation. In contrast, IL-7 induces development of a population of T cells that produce large amounts of IL-4. Growth in IL-7 also increases IL-2-induced production of interferon (IFN)-gamma and IL-10 production. IL-7-induced IL-4 production is not inhibited by neutralizing antibodies to IL-4 on its receptor. This implies that IL-7 acts directly to induce Th2 subset development and not by up-regulating either production of IL-4 during culture or expression of the IL-4 receptor. Moreover, IL-7 potentiates the effects of CD28 co-stimulation on both naive CD4+ cell proliferation and subsequent IL-4 production. Following primary stimulation, CD4+ cells lose expression of the IL-7 receptor, resulting in IL-7 unresponsiveness. This work reveals a novel role for IL-7 in the primary activation of CD4+ cells. We propose that in conjunction with CD28 co-stimulation, IL-7 induces the initial expression of IL-4 production and that IL-4 acts subsequently to expand Th2 cytokine-producing cells at the appropriate anatomical site. |
| spellingShingle | Webb, L Foxwell, B Feldmann, M Interleukin-7 activates human naive CD4+ cells and primes for interleukin-4 production. |
| title | Interleukin-7 activates human naive CD4+ cells and primes for interleukin-4 production. |
| title_full | Interleukin-7 activates human naive CD4+ cells and primes for interleukin-4 production. |
| title_fullStr | Interleukin-7 activates human naive CD4+ cells and primes for interleukin-4 production. |
| title_full_unstemmed | Interleukin-7 activates human naive CD4+ cells and primes for interleukin-4 production. |
| title_short | Interleukin-7 activates human naive CD4+ cells and primes for interleukin-4 production. |
| title_sort | interleukin 7 activates human naive cd4 cells and primes for interleukin 4 production |
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