Mice transgenic for a soluble form of murine CTLA-4 show enhanced expansion of antigen-specific CD4+ T cells and defective antibody production in vivo - PubMed (original) (raw)
Mice transgenic for a soluble form of murine CTLA-4 show enhanced expansion of antigen-specific CD4+ T cells and defective antibody production in vivo
F Ronchese et al. J Exp Med. 1994.
Abstract
CD4+ T cell responses were analyzed in transgenic mice expressing a soluble form of murine CTLA-4, mCTLA4-H gamma 1, which blocks the interaction of the T cell activation molecules CD28 and CTLA-4 with their costimulatory ligands. Consistent with previous reports (Linsley, P. S., P. M. Wallace, J. Johnson, M. G. Gibson, J. L. Greene, J. A. Ledbetter, C. Singh, and M. A. Tepper. 1992. Science (Wash. DC). 257:792), T cell-dependent antibody production was profoundly inhibited in mCTLA4-H gamma 1 transgenic mice immunized with a protein antigen. Surprisingly, however, transgenic mice could generate quantitatively and qualitatively normal primary T cell responses, as measured by limiting dilution assays and lymphokine production. In addition, in vivo expansion of antigen-specific T cells after secondary or tertiary immunization was enhanced in mCTLA4-H gamma 1 transgenics as compared with normal mice. Although unable to deliver cognate help to B cells in vivo, T cells from mCTLA4-H gamma 1 transgenic mice were not anergic as they could help B cells to produce specific antibodies when adoptively transferred into nude hosts. Taken together, these data suggest that the engagement of CD28 and/or CTLA-4 may not be required for the induction of T cell responses, as is currently understood, but rather for the expression of T cell effector function such as the delivery of T cell help to B cells.
Similar articles
- B cell function in mice transgenic for mCTLA4-H gamma 1: lack of germinal centers correlated with poor affinity maturation and class switching despite normal priming of CD4+ T cells.
Lane P, Burdet C, Hubele S, Scheidegger D, Müller U, McConnell F, Kosco-Vilbois M. Lane P, et al. J Exp Med. 1994 Mar 1;179(3):819-30. doi: 10.1084/jem.179.3.819. J Exp Med. 1994. PMID: 7509361 Free PMC article. - Coexpression and functional cooperation of CTLA-4 and CD28 on activated T lymphocytes.
Linsley PS, Greene JL, Tan P, Bradshaw J, Ledbetter JA, Anasetti C, Damle NK. Linsley PS, et al. J Exp Med. 1992 Dec 1;176(6):1595-604. doi: 10.1084/jem.176.6.1595. J Exp Med. 1992. PMID: 1334116 Free PMC article. - Blockade of T cell activation using a surface-linked single-chain antibody to CTLA-4 (CD152).
Griffin MD, Hong DK, Holman PO, Lee KM, Whitters MJ, O'Herrin SM, Fallarino F, Collins M, Segal DM, Gajewski TF, Kranz DM, Bluestone JA. Griffin MD, et al. J Immunol. 2000 May 1;164(9):4433-42. doi: 10.4049/jimmunol.164.9.4433. J Immunol. 2000. PMID: 10779742 - Blocking CD28/B7 with soluble competitors: immunological phenotype of mCTLA4-H gamma 1 transgenic mice.
Lane P. Lane P. Res Immunol. 1995 Mar-Apr;146(3):176-9. doi: 10.1016/0923-2494(96)80254-9. Res Immunol. 1995. PMID: 8525050 Review. No abstract available. - Expression and functional significance of CTLA-4, a negative regulator of T cell activation.
Kosmaczewska A, Ciszak L, Boćko D, Frydecka I. Kosmaczewska A, et al. Arch Immunol Ther Exp (Warsz). 2001;49(1):39-46. Arch Immunol Ther Exp (Warsz). 2001. PMID: 11266089 Review.
Cited by
- Multifaceted effects of soluble human CD6 in experimental cancer models.
Simões IT, Aranda F, Casadó-Llombart S, Velasco-de Andrés M, Català C, Álvarez P, Consuegra-Fernández M, Orta-Mascaró M, Merino R, Merino J, Alberola-Ila J, González-Aseguinolaza G, Carreras E, Martínez V, Lozano F. Simões IT, et al. J Immunother Cancer. 2020 Mar;8(1):e000172. doi: 10.1136/jitc-2019-000172. J Immunother Cancer. 2020. PMID: 32217757 Free PMC article. - Transgenic expression of soluble human CD5 enhances experimentally-induced autoimmune and anti-tumoral immune responses.
Fenutría R, Martinez VG, Simões I, Postigo J, Gil V, Martínez-Florensa M, Sintes J, Naves R, Cashman KS, Alberola-Ila J, Ramos-Casals M, Soldevila G, Raman C, Merino J, Merino R, Engel P, Lozano F. Fenutría R, et al. PLoS One. 2014 Jan 15;9(1):e84895. doi: 10.1371/journal.pone.0084895. eCollection 2014. PLoS One. 2014. PMID: 24454761 Free PMC article. - Anti-CTLA-4 treatment induces IL-10-producing ICOS+ regulatory T cells displaying IDO-dependent anti-inflammatory properties in a mouse model of colitis.
Coquerelle C, Oldenhove G, Acolty V, Denoeud J, Vansanten G, Verdebout JM, Mellor A, Bluestone JA, Moser M. Coquerelle C, et al. Gut. 2009 Oct;58(10):1363-73. doi: 10.1136/gut.2008.162842. Epub 2009 Jun 7. Gut. 2009. PMID: 19505881 Free PMC article. - Translating costimulation blockade to the clinic: lessons learned from three pathways.
Ford ML, Larsen CP. Ford ML, et al. Immunol Rev. 2009 May;229(1):294-306. doi: 10.1111/j.1600-065X.2009.00776.x. Immunol Rev. 2009. PMID: 19426229 Free PMC article. Review. - Th2 cells and cytokine networks in allergic inflammation of the lung.
Coyle AJ, Tsuyuki S. Coyle AJ, et al. Mediators Inflamm. 1995;4(4):239-47. doi: 10.1155/S096293519500038X. Mediators Inflamm. 1995. PMID: 18475645 Free PMC article.
References
- Annu Rev Immunol. 1989;7:445-80 - PubMed
- J Exp Med. 1979 Jan 1;149(1):1-16 - PubMed
- J Immunol. 1990 Jan 1;144(1):16-22 - PubMed
- J Exp Med. 1990 May 1;171(5):1753-71 - PubMed
- Immunol Today. 1990 Jun;11(6):211-6 - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials