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Tfh and Tfr Cells in Autoimmune Diseases

Year 2023, Volume: 6 Issue: 4, 735 - 739, 15.10.2023
https://doi.org/10.19127/bshealthscience.1298421

Abstract

An immunological condition known as autoimmunity causes the excessive generation of autoantibodies against self-antigen and is characterized by enhanced T-cell activation and extra-stimulated B-cells. The development of lymphatic follicle germinal centers (GCs), the maturation of B cells, and differentiation into plasma cells are all significantly aided by follicular helper T cells (Tfh). Tfh cells express the transcriptional regulator B cell lymphoma 6 (BCL-6), C-X-C chemokine receptor 5 (CXCR5), inducible T cell co-stimulator (ICOS), and programmed cell death protein 1 (PD-1). The production of interleukin (IL)-21 and low expression of the chemokine (C-C motif) receptor 7 (CCR7) define Tfh cells. Additionally, Tfh cells are a diverse population of cells with the potential to co-express minute quantities of transcription factors, such as T-box expressed in T cells (T-bet), GATA-binding protein 3 (GATA-3), and retinoic acid receptor-related orphan receptor (ROR-t). Tfh cells that also produce IL-21, IL-4, IL-17, and IFN-γ are referred to as Tfh1, Tfh2, and Tfh17 cells, respectively. The control of humoral immunity is carried out by follicular regulatory (Tfr) cells that express Forkhead box protein 3 (Foxp3). Tfr cells can, however, decrease T-B cell interactions through the cytotoxic T lymphocyte-associated protein 4 (CTLA-4) while promoting B cell maturation through IL-10. In the context of autoimmunity, the role of Tfh and Tfr cells is still not fully understood. We intend to present the most recent data on the characteristics and function of Tfh and Tfr cells under conditions of autoimmunity in this review.

References

  • Botta D, Fuller MJ, Marquez-Lago TT, Bachus H, Bradley JE, Weinmann AS, Zajac AJ, Randall TD, Lund FE, Leon B, Ballesteros-Tato A. 2017. Dynamic regulation of T follicular regulatory cell responses by interleukin 2 during influenza infection. Nature Immunol, 18(11): 1249-1260.
  • Breitfeld D, Ohl L, Kremmer E, Ellwart J, Sallusto F, Lipp M, Förster R. 2000. Follicular B helper T cells express CXC chemokine receptor 5, localize to B cell follicles, and support immunoglobulin production. J Experiment Med, 192(11): 1545-1552.
  • Chao G, Li X, Ji Y, Zhu Y, Li N, Zhang N, Feng Z, Niu M. 2018. CTLA-4 regulates T follicular regulatory cell differentiation and participates in intestinal damage caused by spontaneous autoimmunity. Biochemical and biophysical research communications, 505(3): 865-871.
  • Choi YS, Kageyama R, Eto D, Escobar TC, Johnston RJ, Monticelli L, Lao C, Crotty S. 2011. ICOS receptor instructs T follicular helper cell versus effector cell differentiation via induction of the transcriptional repressor Bcl6. Immunity, 34(6): 932-946.
  • Chung Y, Tanaka S, Chu F, Nurieva RI, Martinez GJ, Rawal S, Wang YH, Lim H, Reynolds JM, Zhou XH, Fan HM, Liu ZM, Neelapu SS, Dong C. 2011. Follicular regulatory T cells expressing Foxp3 and Bcl-6 suppress germinal center reactions. Nature Med, 17(8): 983-988.
  • Craft JE. 2012. Follicular helper T cells in immunity and systemic autoimmunity. Nature Reviews Rheumatology, 8(6): 337-347.
  • Crotty S. 2014. T follicular helper cell differentiation, function, and roles in disease. Immunity, 41(4): 529-542.
  • Crotty S. 2019. T follicular helper cell biology: a decade of discovery and diseases. Immunity, 50(5): 1132-1148.
  • Goverman JM. 2021. Regulatory T cells in multiple sclerosis. New England J Med, 384(6): 578-580.
  • Hogquist KA, Jameson SC. 2014. The self-obsession of T cells: how TCR signaling thresholds affect fate'decisions' and effector function. Nature Immunol, 15(9): 815-823.
  • Humby F, Bombardieri M, Manzo A, Kelly S, Blades MC, Kirkham B, Spencer J, Pitzalis C. 2009. Ectopic lymphoid structures support ongoing production of class-switched autoantibodies in rheumatoid synovium. PLoS Med, 6(1): e1.
  • Hutloff A. 2018. T follicular helper-like cells in inflamed non-lymphoid tissues. Front Immunol, 9: 1707.
  • Jogdand GM, Mohanty S, Devadas S. 2016. Regulators of Tfh cell differentiation. Front Immunol, 7: 520.
  • Johnston RJ, Poholek AC, DiToro D, Yusuf I, Eto D, Barnett B, Dent A, Craft J, Crotty S. 2009. Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of T follicular helper cell differentiation. Science, 325(5943): 1006-1010.
  • Kräutler NJ, Suan D, Butt D, Bourne K, Hermes JR, Chan TD, Sundling C, Kaplan W, Schofield P, Jackson J, Basten A, Christ D, Brink R. 2017. Differentiation of germinal center B cells into plasma cells is initiated by high-affinity antigen and completed by Tfh cells. J Experiment Med, 214(5): 1259-1267.
  • Krumbholz M, Theil D, Cepok S, Hemmer B, Kivisäkk P, Ransohoff RM, Hofbauer M, Farina C, Derfuss T, Hartle C, Newcombe J, Hohlfeld R, Meinl E. 2006. Chemokines in multiple sclerosis: CXCL12 and CXCL13 up-regulation is differentially linked to CNS immune cell recruitment. Brain, 129(1): 200-211.
  • Laguna-Goya R, Suàrez-Fernández P, Paz-Artal E. 2019. Follicular helper T cells and humoral response in organ transplantation. Transplant Rev, 33(4): 183-190.
  • Laidlaw BJ, Lu Y, Amezquita RA, Weinstein JS, Vander Heiden JA, Gupta NT, Kleinstein SH, Kaech SM, Craft J. 2017. Interleukin-10 from CD4+ follicular regulatory T cells promotes the germinal center response. Sci Immunol, 2(16): eaan4767.
  • Linterman MA, Pierson W, Lee SK, Kallies A, Kawamoto S, Rayner TF, Srivastava M, Divekar DP, Beaton L, Hogan JJ, Fagarasan S, Liston A, Smith KGC, Vinuesa CG. 2011. Foxp3+ follicular regulatory T cells control the germinal center response. Nature Med, 17(8): 975-982.
  • Linterman MA, Rigby RJ, Wong RK, Yu D, Brink R, Cannons JL, Schwartzberg PL, Cook MC, Walters GD, Vinuesa CG. 2009. Follicular helper T cells are required for systemic autoimmunity. J Experimental Med, 206(3): 561-576.
  • Liu X, Chen X, Zhong B, Wang A, Wang X, Chu F, Nurieva R, Yan X, Chen P, van der Flier LG, Nakatsukasa H, Neelapu SS, Chen W, Clevers H, Tian Q, Qi H, Wei L, Dong C. 2014. Transcription factor achaete-scute homologue 2 initiates follicular T-helper-cell development. Nature, 507(7493): 513-518.
  • Ma CS, Deenick EK, Batten M, Tangye SG. 2012. The origins, function, and regulation of T follicular helper cells. J Experimental Med, 209(7): 1241-1253.
  • Ren HM, Lukacher AE, Rahman ZS, Olsen NJ. 2021. New developments implicating IL-21 in autoimmune disease. J Autoimmun, 122: 102689.
  • Sage PT, Francisco LM, Carman CV, Sharpe AH. 2013. The receptor PD-1 controls follicular regulatory T cells in the lymph nodes and blood. Nature Immunol, 14(2): 152-161.
  • Sage PT, Paterson AM, Lovitch SB, Sharpe AH. 2014. The coinhibitory receptor CTLA-4 controls B cell responses by modulating T follicular helper, T follicular regulatory, and T regulatory cells. Immunity, 41(6): 1026-1039.
  • Sage PT, Sharpe AH. 2015. T follicular regulatory cells in the regulation of B cell responses. Trends Immunol, 36(7): 410-418.
  • Sage PT, Sharpe AH. 2016. T follicular regulatory cells. Immunological Reviews, 271(1): 246-259.
  • Sage PT, Sharpe AH. 2020. The multifaceted functions of follicular regulatory T cells. Current Opin Immunol, 67: 68-74.
  • Schaerli P, Willimann K, Lang AB, Lipp M, Loetscher P, Moser B. 2000. CXC chemokine receptor 5 expression defines follicular homing T cells with B cell helper function. J Experiment Med, 192(11): 1553-1562.
  • Schmitt N, Bentebibel SE, Ueno H. 2014. Phenotype and functions of memory Tfh cells in human blood. Trends Immunol, 35(9): 436-442.
  • Simpson N, Gatenby PA, Wilson A, Malik S, Fulcher DA, Tangye SG, Manku H, Vyse TJ, Roncador G, Huttley GA, Goodnow CC, Vinuesa CG, Cook MC. 2010. Expansion of circulating T cells resembling follicular helper T cells is a fixed phenotype that identifies a subset of severe systemic lupus erythematosus. J American College Rheumatol, 62(1): 234-244.
  • Stebegg M, Kumar SD, Silva-Cayetano A, Fonseca VR, Linterman MA, Graca L. 2018. Regulation of the germinal center response. Front Immunol, 2469.
  • Tangye SG, Ma CS, Brink R, Deenick EK. 2013. The good, the bad and the ugly—TFH cells in human health and disease. Nature Rev Immunol, 13(6): 412-426.
  • Vinuesa CG, Linterman MA, Yu D, MacLennan IC. 2016. Follicular helper T cells. Annual Rev Immunol, 34: 335-368.
  • Watanabe R, Fujimoto M, Ishiura N, Kuwano Y, Nakashima H, Yazawa N, Okochi H, Sato S, Tedder TF, Tamaki K. 2007. CD19 expression in B cells is important for suppression of contact hypersensitivity. The American J Pathol, 171(2): 560-570.
  • Webb LM, Linterman MA. 2017. Signals that drive T follicular helper cell formation. Immunol, 152(2): 185-194.
  • Wing JB, Sakaguchi S. 2014. Foxp3+ Treg cells in humoral immunity. Inter Immunol, 26(2): 61-69.
  • Wing JB, Sakaguchi S. 2018. T follicular regulatory cells emerge in the GC. Cell Immunol, 333: 96-99.
  • Wing JB, Tanaka A, Sakaguchi S. 2019. Human FOXP3+ regulatory T cell heterogeneity and function in autoimmunity and cancer. Immun, 50(2): 302-316.
  • Wing K, Onishi Y, Prieto-Martin P, Yamaguchi T, Miyara M, Fehervari Z, Nomura T, Sakaguchi S. 2008. CTLA-4 control over Foxp3+ regulatory T cell function. Sci, 322(5899): 271-275.
  • Wollenberg I, Agua-Doce A, Hernández A, Almeida C, Oliveira VG, Faro J, Graca L. 2011. Regulation of the germinal center reaction by Foxp3+ follicular regulatory T cells. J Immunol, 187(9): 4553-4560.
  • Wojciechowicz K, Spodzieja M, Lisowska KA, Wardowska A. 2022. The role of the BTLA-HVEM complex in the pathogenesis of autoimmune diseases. Cellular Immunol, 104532.

Tfh and Tfr Cells in Autoimmune Diseases

Year 2023, Volume: 6 Issue: 4, 735 - 739, 15.10.2023
https://doi.org/10.19127/bshealthscience.1298421

Abstract

An immunological condition known as autoimmunity causes the excessive generation of autoantibodies against self-antigen and is characterized by enhanced T-cell activation and extra-stimulated B-cells. The development of lymphatic follicle germinal centers (GCs), the maturation of B cells, and differentiation into plasma cells are all significantly aided by follicular helper T cells (Tfh). Tfh cells express the transcriptional regulator B cell lymphoma 6 (BCL-6), C-X-C chemokine receptor 5 (CXCR5), inducible T cell co-stimulator (ICOS), and programmed cell death protein 1 (PD-1). The production of interleukin (IL)-21 and low expression of the chemokine (C-C motif) receptor 7 (CCR7) define Tfh cells. Additionally, Tfh cells are a diverse population of cells with the potential to co-express minute quantities of transcription factors, such as T-box expressed in T cells (T-bet), GATA-binding protein 3 (GATA-3), and retinoic acid receptor-related orphan receptor (ROR-t). Tfh cells that also produce IL-21, IL-4, IL-17, and IFN-γ are referred to as Tfh1, Tfh2, and Tfh17 cells, respectively. The control of humoral immunity is carried out by follicular regulatory (Tfr) cells that express Forkhead box protein 3 (Foxp3). Tfr cells can, however, decrease T-B cell interactions through the cytotoxic T lymphocyte-associated protein 4 (CTLA-4) while promoting B cell maturation through IL-10. In the context of autoimmunity, the role of Tfh and Tfr cells is still not fully understood. We intend to present the most recent data on the characteristics and function of Tfh and Tfr cells under conditions of autoimmunity in this review.

References

  • Botta D, Fuller MJ, Marquez-Lago TT, Bachus H, Bradley JE, Weinmann AS, Zajac AJ, Randall TD, Lund FE, Leon B, Ballesteros-Tato A. 2017. Dynamic regulation of T follicular regulatory cell responses by interleukin 2 during influenza infection. Nature Immunol, 18(11): 1249-1260.
  • Breitfeld D, Ohl L, Kremmer E, Ellwart J, Sallusto F, Lipp M, Förster R. 2000. Follicular B helper T cells express CXC chemokine receptor 5, localize to B cell follicles, and support immunoglobulin production. J Experiment Med, 192(11): 1545-1552.
  • Chao G, Li X, Ji Y, Zhu Y, Li N, Zhang N, Feng Z, Niu M. 2018. CTLA-4 regulates T follicular regulatory cell differentiation and participates in intestinal damage caused by spontaneous autoimmunity. Biochemical and biophysical research communications, 505(3): 865-871.
  • Choi YS, Kageyama R, Eto D, Escobar TC, Johnston RJ, Monticelli L, Lao C, Crotty S. 2011. ICOS receptor instructs T follicular helper cell versus effector cell differentiation via induction of the transcriptional repressor Bcl6. Immunity, 34(6): 932-946.
  • Chung Y, Tanaka S, Chu F, Nurieva RI, Martinez GJ, Rawal S, Wang YH, Lim H, Reynolds JM, Zhou XH, Fan HM, Liu ZM, Neelapu SS, Dong C. 2011. Follicular regulatory T cells expressing Foxp3 and Bcl-6 suppress germinal center reactions. Nature Med, 17(8): 983-988.
  • Craft JE. 2012. Follicular helper T cells in immunity and systemic autoimmunity. Nature Reviews Rheumatology, 8(6): 337-347.
  • Crotty S. 2014. T follicular helper cell differentiation, function, and roles in disease. Immunity, 41(4): 529-542.
  • Crotty S. 2019. T follicular helper cell biology: a decade of discovery and diseases. Immunity, 50(5): 1132-1148.
  • Goverman JM. 2021. Regulatory T cells in multiple sclerosis. New England J Med, 384(6): 578-580.
  • Hogquist KA, Jameson SC. 2014. The self-obsession of T cells: how TCR signaling thresholds affect fate'decisions' and effector function. Nature Immunol, 15(9): 815-823.
  • Humby F, Bombardieri M, Manzo A, Kelly S, Blades MC, Kirkham B, Spencer J, Pitzalis C. 2009. Ectopic lymphoid structures support ongoing production of class-switched autoantibodies in rheumatoid synovium. PLoS Med, 6(1): e1.
  • Hutloff A. 2018. T follicular helper-like cells in inflamed non-lymphoid tissues. Front Immunol, 9: 1707.
  • Jogdand GM, Mohanty S, Devadas S. 2016. Regulators of Tfh cell differentiation. Front Immunol, 7: 520.
  • Johnston RJ, Poholek AC, DiToro D, Yusuf I, Eto D, Barnett B, Dent A, Craft J, Crotty S. 2009. Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of T follicular helper cell differentiation. Science, 325(5943): 1006-1010.
  • Kräutler NJ, Suan D, Butt D, Bourne K, Hermes JR, Chan TD, Sundling C, Kaplan W, Schofield P, Jackson J, Basten A, Christ D, Brink R. 2017. Differentiation of germinal center B cells into plasma cells is initiated by high-affinity antigen and completed by Tfh cells. J Experiment Med, 214(5): 1259-1267.
  • Krumbholz M, Theil D, Cepok S, Hemmer B, Kivisäkk P, Ransohoff RM, Hofbauer M, Farina C, Derfuss T, Hartle C, Newcombe J, Hohlfeld R, Meinl E. 2006. Chemokines in multiple sclerosis: CXCL12 and CXCL13 up-regulation is differentially linked to CNS immune cell recruitment. Brain, 129(1): 200-211.
  • Laguna-Goya R, Suàrez-Fernández P, Paz-Artal E. 2019. Follicular helper T cells and humoral response in organ transplantation. Transplant Rev, 33(4): 183-190.
  • Laidlaw BJ, Lu Y, Amezquita RA, Weinstein JS, Vander Heiden JA, Gupta NT, Kleinstein SH, Kaech SM, Craft J. 2017. Interleukin-10 from CD4+ follicular regulatory T cells promotes the germinal center response. Sci Immunol, 2(16): eaan4767.
  • Linterman MA, Pierson W, Lee SK, Kallies A, Kawamoto S, Rayner TF, Srivastava M, Divekar DP, Beaton L, Hogan JJ, Fagarasan S, Liston A, Smith KGC, Vinuesa CG. 2011. Foxp3+ follicular regulatory T cells control the germinal center response. Nature Med, 17(8): 975-982.
  • Linterman MA, Rigby RJ, Wong RK, Yu D, Brink R, Cannons JL, Schwartzberg PL, Cook MC, Walters GD, Vinuesa CG. 2009. Follicular helper T cells are required for systemic autoimmunity. J Experimental Med, 206(3): 561-576.
  • Liu X, Chen X, Zhong B, Wang A, Wang X, Chu F, Nurieva R, Yan X, Chen P, van der Flier LG, Nakatsukasa H, Neelapu SS, Chen W, Clevers H, Tian Q, Qi H, Wei L, Dong C. 2014. Transcription factor achaete-scute homologue 2 initiates follicular T-helper-cell development. Nature, 507(7493): 513-518.
  • Ma CS, Deenick EK, Batten M, Tangye SG. 2012. The origins, function, and regulation of T follicular helper cells. J Experimental Med, 209(7): 1241-1253.
  • Ren HM, Lukacher AE, Rahman ZS, Olsen NJ. 2021. New developments implicating IL-21 in autoimmune disease. J Autoimmun, 122: 102689.
  • Sage PT, Francisco LM, Carman CV, Sharpe AH. 2013. The receptor PD-1 controls follicular regulatory T cells in the lymph nodes and blood. Nature Immunol, 14(2): 152-161.
  • Sage PT, Paterson AM, Lovitch SB, Sharpe AH. 2014. The coinhibitory receptor CTLA-4 controls B cell responses by modulating T follicular helper, T follicular regulatory, and T regulatory cells. Immunity, 41(6): 1026-1039.
  • Sage PT, Sharpe AH. 2015. T follicular regulatory cells in the regulation of B cell responses. Trends Immunol, 36(7): 410-418.
  • Sage PT, Sharpe AH. 2016. T follicular regulatory cells. Immunological Reviews, 271(1): 246-259.
  • Sage PT, Sharpe AH. 2020. The multifaceted functions of follicular regulatory T cells. Current Opin Immunol, 67: 68-74.
  • Schaerli P, Willimann K, Lang AB, Lipp M, Loetscher P, Moser B. 2000. CXC chemokine receptor 5 expression defines follicular homing T cells with B cell helper function. J Experiment Med, 192(11): 1553-1562.
  • Schmitt N, Bentebibel SE, Ueno H. 2014. Phenotype and functions of memory Tfh cells in human blood. Trends Immunol, 35(9): 436-442.
  • Simpson N, Gatenby PA, Wilson A, Malik S, Fulcher DA, Tangye SG, Manku H, Vyse TJ, Roncador G, Huttley GA, Goodnow CC, Vinuesa CG, Cook MC. 2010. Expansion of circulating T cells resembling follicular helper T cells is a fixed phenotype that identifies a subset of severe systemic lupus erythematosus. J American College Rheumatol, 62(1): 234-244.
  • Stebegg M, Kumar SD, Silva-Cayetano A, Fonseca VR, Linterman MA, Graca L. 2018. Regulation of the germinal center response. Front Immunol, 2469.
  • Tangye SG, Ma CS, Brink R, Deenick EK. 2013. The good, the bad and the ugly—TFH cells in human health and disease. Nature Rev Immunol, 13(6): 412-426.
  • Vinuesa CG, Linterman MA, Yu D, MacLennan IC. 2016. Follicular helper T cells. Annual Rev Immunol, 34: 335-368.
  • Watanabe R, Fujimoto M, Ishiura N, Kuwano Y, Nakashima H, Yazawa N, Okochi H, Sato S, Tedder TF, Tamaki K. 2007. CD19 expression in B cells is important for suppression of contact hypersensitivity. The American J Pathol, 171(2): 560-570.
  • Webb LM, Linterman MA. 2017. Signals that drive T follicular helper cell formation. Immunol, 152(2): 185-194.
  • Wing JB, Sakaguchi S. 2014. Foxp3+ Treg cells in humoral immunity. Inter Immunol, 26(2): 61-69.
  • Wing JB, Sakaguchi S. 2018. T follicular regulatory cells emerge in the GC. Cell Immunol, 333: 96-99.
  • Wing JB, Tanaka A, Sakaguchi S. 2019. Human FOXP3+ regulatory T cell heterogeneity and function in autoimmunity and cancer. Immun, 50(2): 302-316.
  • Wing K, Onishi Y, Prieto-Martin P, Yamaguchi T, Miyara M, Fehervari Z, Nomura T, Sakaguchi S. 2008. CTLA-4 control over Foxp3+ regulatory T cell function. Sci, 322(5899): 271-275.
  • Wollenberg I, Agua-Doce A, Hernández A, Almeida C, Oliveira VG, Faro J, Graca L. 2011. Regulation of the germinal center reaction by Foxp3+ follicular regulatory T cells. J Immunol, 187(9): 4553-4560.
  • Wojciechowicz K, Spodzieja M, Lisowska KA, Wardowska A. 2022. The role of the BTLA-HVEM complex in the pathogenesis of autoimmune diseases. Cellular Immunol, 104532.
There are 42 citations in total.

Details

Primary Language English
Subjects Clinical Sciences
Journal Section Review
Authors

Gulam Hekimoğlu 0000-0002-5027-6756

Nurullah Yücel 0000-0003-2689-4287

Muzaffer Şeker 0000-0002-6815-2540

Early Pub Date September 8, 2023
Publication Date October 15, 2023
Submission Date May 17, 2023
Acceptance Date August 14, 2023
Published in Issue Year 2023 Volume: 6 Issue: 4

Cite

APA Hekimoğlu, G., Yücel, N., & Şeker, M. (2023). Tfh and Tfr Cells in Autoimmune Diseases. Black Sea Journal of Health Science, 6(4), 735-739. https://doi.org/10.19127/bshealthscience.1298421
AMA Hekimoğlu G, Yücel N, Şeker M. Tfh and Tfr Cells in Autoimmune Diseases. BSJ Health Sci. October 2023;6(4):735-739. doi:10.19127/bshealthscience.1298421
Chicago Hekimoğlu, Gulam, Nurullah Yücel, and Muzaffer Şeker. “Tfh and Tfr Cells in Autoimmune Diseases”. Black Sea Journal of Health Science 6, no. 4 (October 2023): 735-39. https://doi.org/10.19127/bshealthscience.1298421.
EndNote Hekimoğlu G, Yücel N, Şeker M (October 1, 2023) Tfh and Tfr Cells in Autoimmune Diseases. Black Sea Journal of Health Science 6 4 735–739.
IEEE G. Hekimoğlu, N. Yücel, and M. Şeker, “Tfh and Tfr Cells in Autoimmune Diseases”, BSJ Health Sci., vol. 6, no. 4, pp. 735–739, 2023, doi: 10.19127/bshealthscience.1298421.
ISNAD Hekimoğlu, Gulam et al. “Tfh and Tfr Cells in Autoimmune Diseases”. Black Sea Journal of Health Science 6/4 (October 2023), 735-739. https://doi.org/10.19127/bshealthscience.1298421.
JAMA Hekimoğlu G, Yücel N, Şeker M. Tfh and Tfr Cells in Autoimmune Diseases. BSJ Health Sci. 2023;6:735–739.
MLA Hekimoğlu, Gulam et al. “Tfh and Tfr Cells in Autoimmune Diseases”. Black Sea Journal of Health Science, vol. 6, no. 4, 2023, pp. 735-9, doi:10.19127/bshealthscience.1298421.
Vancouver Hekimoğlu G, Yücel N, Şeker M. Tfh and Tfr Cells in Autoimmune Diseases. BSJ Health Sci. 2023;6(4):735-9.