Protective Immunity to Nematode Infection is Induced by CTLA-4 Blockade

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 1997 Jul 21

PMID 9221747

Citations 32

Authors

K McCoy

M Camberis

G L Gros

Affiliations

Soon will be listed here.

Abstract

The recent observation that neutralization or genetic deletion of the T lymphocyte receptor CTLA-4 allows enhanced T cell reactivity offers new opportunities for immunotherapy against infectious agents. We used a neutralizing antibody to block CTLA-4 interaction with its ligands CD80 and CD86 during infection of mice with the nematode, Nippostrongylus brasiliensis. CTLA-4 blockade greatly enhanced and accelerated the T cell immune response to N. brasiliensis, resulting in a profound reduction in adult worm numbers and early termination of parasite egg production. The ability of CTLA-4 blockade to accelerate primary immune responses to a protective level during an acute infection indicates its potential as an immunotherapeutic tool for dealing with infectious agents.

Citing Articles

Cytotoxic T-Lymphocyte-Associated Antigen 4 (CTLA-4)- and Programmed Death 1 (PD-1)-Mediated Regulation of Monofunctional and Dual Functional CD4 and CD8 T-Cell Responses in a Chronic Helminth Infection.

Rajamanickam A, Munisankar S, Dolla C, Nutman T, Babu S Infect Immun. 2019; 87(12).

PMID: 31570560 PMC: 6867839. DOI: 10.1128/IAI.00469-19.

PD-L1, TIM-3, and CTLA-4 Blockade Fails To Promote Resistance to Secondary Infection with Virulent Strains of Toxoplasma gondii.

Splitt S, Souza S, Valentine K, Castellanos B, Curd A, Hoyer K Infect Immun. 2018; 86(9).

PMID: 29967089 PMC: 6105904. DOI: 10.1128/IAI.00459-18.

Increased CTLA-4 T cells may contribute to impaired T helper type 1 immune responses in patients with chronic obstructive pulmonary disease.

Tan D, Teo T, Setiawan A, Ong N, Zimmermann M, Price P Immunology. 2017; 151(2):219-226.

PMID: 28190271 PMC: 5418458. DOI: 10.1111/imm.12725.

Acute Malaria Induces PD1+CTLA4+ Effector T Cells with Cell-Extrinsic Suppressor Function.

Mackroth M, Abel A, Steeg C, Schulze Zur Wiesch J, Jacobs T PLoS Pathog. 2016; 12(11):e1005909.

PMID: 27802341 PMC: 5089727. DOI: 10.1371/journal.ppat.1005909.

Beyond adjuvants: immunomodulation strategies to enhance T cell immunity.

Kamphorst A, Araki K, Ahmed R Vaccine. 2015; 33 Suppl 2:B21-8.

PMID: 26022562 PMC: 4449453. DOI: 10.1016/j.vaccine.2014.12.082.

References

Ogilvie B, Jones V . Parasitological review. Nippostrongylus brasiliensis: a review of immunity and host-parasite relationship in the rat. Exp Parasitol. 1971; 29(1):138-77. DOI: 10.1016/0014-4894(71)90021-x. View

Walunas T, Lenschow D, Bakker C, Linsley P, Freeman G, Green J . CTLA-4 can function as a negative regulator of T cell activation. Immunity. 1994; 1(5):405-13. DOI: 10.1016/1074-7613(94)90071-x. View

Coffman R, Seymour B, Hudak S, Jackson J, Rennick D . Antibody to interleukin-5 inhibits helminth-induced eosinophilia in mice. Science. 1989; 245(4915):308-10. DOI: 10.1126/science.2787531. View

Madden K, Urban Jr J, Ziltener H, Schrader J, Finkelman F, Katona I . Antibodies to IL-3 and IL-4 suppress helminth-induced intestinal mastocytosis. J Immunol. 1991; 147(4):1387-91. View

Urban Jr J, Madden K, Svetic A, Cheever A, Trotta P, Gause W . The importance of Th2 cytokines in protective immunity to nematodes. Immunol Rev. 1992; 127:205-20. DOI: 10.1111/j.1600-065x.1992.tb01415.x. View

Linsley P, Greene J, Tan P, Bradshaw J, Ledbetter J, Anasetti C . Coexpression and functional cooperation of CTLA-4 and CD28 on activated T lymphocytes. J Exp Med. 1992; 176(6):1595-604. PMC: 2119471. DOI: 10.1084/jem.176.6.1595. View

Krummel M, Allison J . CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation. J Exp Med. 1995; 182(2):459-65. PMC: 2192127. DOI: 10.1084/jem.182.2.459. View

Kearney E, Walunas T, Karr R, Morton P, Loh D, Bluestone J . Antigen-dependent clonal expansion of a trace population of antigen-specific CD4+ T cells in vivo is dependent on CD28 costimulation and inhibited by CTLA-4. J Immunol. 1995; 155(3):1032-6. View

Allison J, Krummel M . The Yin and Yang of T cell costimulation. Science. 1995; 270(5238):932-3. DOI: 10.1126/science.270.5238.932. View

10.

Waterhouse P, Penninger J, Timms E, Wakeham A, Shahinian A, Lee K . Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4. Science. 1995; 270(5238):985-8. DOI: 10.1126/science.270.5238.985. View

11.

Tivol E, Borriello F, Schweitzer A, Lynch W, Bluestone J, Sharpe A . Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4. Immunity. 1995; 3(5):541-7. DOI: 10.1016/1074-7613(95)90125-6. View

12.

Krummel M, Allison J . CTLA-4 engagement inhibits IL-2 accumulation and cell cycle progression upon activation of resting T cells. J Exp Med. 1996; 183(6):2533-40. PMC: 2192613. DOI: 10.1084/jem.183.6.2533. View

13.

Walunas T, Bakker C, Bluestone J . CTLA-4 ligation blocks CD28-dependent T cell activation. J Exp Med. 1996; 183(6):2541-50. PMC: 2192609. DOI: 10.1084/jem.183.6.2541. View

14.

Krummel M, Sullivan T, Allison J . Superantigen responses and co-stimulation: CD28 and CTLA-4 have opposing effects on T cell expansion in vitro and in vivo. Int Immunol. 1996; 8(4):519-23. DOI: 10.1093/intimm/8.4.519. View

15.

Kopf M, Le Gros G, Bachmann M, Lamers M, Bluethmann H, Kohler G . Disruption of the murine IL-4 gene blocks Th2 cytokine responses. Nature. 1993; 362(6417):245-8. DOI: 10.1038/362245a0. View

16.

Urban Jr J, Madden K, CHEEVER A, Trotta P, Katona I, Finkelman F . IFN inhibits inflammatory responses and protective immunity in mice infected with the nematode parasite, Nippostrongylus brasiliensis. J Immunol. 1993; 151(12):7086-94. View

17.

Katona I, Urban Jr J, Finkelman F . The role of L3T4+ and Lyt-2+ T cells in the IgE response and immunity to Nippostrongylus brasiliensis. J Immunol. 1988; 140(9):3206-11. View