CHARACTERIZATION OF CENTRAL AND EFFECTOR CD4⁺ MEMORY CELLS IN PSORIASIS
https://doi.org/10.15789/1563-0625-COC-2288
Abstract
Psoriasis is a chronic autoimmune disease in which the skin and joints are involved in the pathological process. It was found that the recurrence of rashes in this disease occurs due to the resident memory cells of the skin. The number of CD4+CCR3+ effector memory cells in peripheral blood correlates with the severity of the disease. Therefore, the aim of our work is to study the phenotype of peripheral blood memory cells in patients with psoriasis.
The study included 6 healthy donors: average age – 45.4 (min – 29, max – 55), women – 3, men – 3; 10 patients with psoriasis: women – 4, men – 6, average age – 37.3 (min – 23, max – 57), of which 5 patients with PASI > 10 and 5 patients with PASI < 10. The exclusion criteria for the study were the presence of autoimmune, oncological and hematological diseases, systemic therapy with immunosuppressive drugs for 1 month. Patients signed informed consent to participate in the study. Isolation of peripheral blood mononuclear cells was performed in a density gradient of ficoll-urographin (p = 1.082 g/L). Then cells were stained with fluorochrome-conjugated monoclonal antibodies to surface markers of central (Tcm) and effector (Tem) CD4+ memory cells (CD4, CD45RO, CD197), the α-chain of the IL-7 receptor (CD127), and the γ-chain of the IL-7 receptor (CD132). Statistical analysis of the data obtained was performed using the Statistica 6.0 software package.
The percent of Tcm in the peripheral blood of donors was 33.4% (in – 18.2, max – 43.7), Tem – 28.7% (min – 13.6, max – 38.9), in patients with psoriasis: Tcm – 28.65% (min – 13.3, max – 59.6), Tem – 21.5% (min – 9.3, max – 38.6). In the peripheral blood of patients with psoriasis, among the central CD4+ memory cells, the proportion of CD127+CD132- -cells is 26.00%, CD127+CD132+ – 1.69%, CD127+CD132- – 69.00%, CD127- CD132+ – 1.94%. Among effector CD4+ memory cells, the proportion of CD127+CD132- -cells is 23.58%, CD127+CD132+ – 1.18%, CD127+CD132- – 69.84%, CD127- CD132+ – 0.70%. A direct correlation was found between the number of CD127- CD132+ central memory cells and the PASI value (r = 0.639, p < 0.05).
In patients with psoriasis, the proportion of central memory cells is higher than in healthy donors, while the number of effector memory cells is lower. A direct correlation was found between the number of central cells expressing the γ-chain of the IL-7 receptor and the severity of the disease. Activated memory cells are characterized by high expression of CD132. It can be assumed that this population of memory cells plays a role in maintaining autoimmune inflammation in patients with this disease, and also participates in the repopulation of skin resident memory cells.
About the Authors
A. V. KolerovaRussian Federation
Postgraduate Student, 630129, Novosibirsk, Kurchatov str., 11/3, apt 15;
Assistant Professor, Novosibirsk
Competing Interests:
D. A. Mikailova
Russian Federation
Assistant Professor, Department of Fundamental Medicine, Zelman Institute of Medicine and Psychology,
Novosibirsk
M. A. Beimanova
Russian Federation
Postgraduate Student,
Moscow
E. A. Blinova
Russian Federation
PhD (Biology), Senior Research Associate, Laboratory of Immunopathology,
Novosibirsk
References
1. Boyman O., Hefti H.P., Conrad C., Nickolof B.J., Suter M., Nestle F.O. Spontaneous development of psoriasis in a new animal model shows an essential role for resident T cells and tumor necrosis factor-alpha. J. Exp. Med., 2004, Vol. 199, no. 5, pp. 731-726.
2. Brinkman C.C., Rouhani S.J., Srinivasan N., Engelhard V.H. Peripheral tissue homing receptors enable T cell entry into lymph nodes and affect the anatomical distribution of memory cells. J. Immunol., 2013, Vol. 191, no. 5, pp. 2412-2425.
3. Casciano F., Diani M., Altomare A., Granucci F., Secchiero P., Banfi G., Reali E. CCR4+ Skin-tropic phenotype as a feature of central memory CD8+ T Cells in healthy subjects and psoriasis patients. Front. Immunol., 2020, Vol. 11, 529. doi: 10.3389/fimmu.2020.00529.
4. Cheuk S., Wikén M., Blomqvist L., Nylén S., Talme T., Ståhle M., Eidsmo L. Epidermal Th22 and Tc17 cells form a localized disease memory in clinically healed psoriasis. J. Immunol., 2014, Vol. 192, no. 7, pp. 3111-3120.
5. Corgnac S., Boutet M., Kfoury M., Naltet C., Mami-Chouaib F. The emerging role of CD8(+) tissue resident memory T (TRM) cells in antitumor immunity: a unique functional contribution of the CD103 integrin. Front. Immunol., 2018, Vol. 9, 1904. doi: 10.3389/fimmu.2018.01904.
6. Ellis C.N., Krueger G.G.; Alefacept Clinical Study Group. Treatment of chronic plaque psoriasis by selective targeting of memory effector T lymphocytes. N. Engl. Med., 2001, Vol. 345, no. 4, pp. 248-255.
7. Fujiyama T., Umayahara T., Kurihara K., Shimauchi T., Ito T., Aoshima M., Otobe E., Hashizume H., Yagi H., Tokura Y. Skin infiltration of pathogenic migratory and resident T Cells is decreased by secukinumab treatment in psoriasis. J. Invest. Dermatol., 2020, Vol. 140, no. 10, pp. 2073-2076.e6.
8. Gaide O., Emerson R.O., Jiang X., Gulati N., Nizza S., Desmarais C., Robins H., Krueger J.G., Clark R.A., Kupper T.S. Common clonal origin of central and resident memory T cells following skin immunization. Nat. Med., 2015, Vol. 21, pp. 647-653.
9. Kunkel E.J., Boisvert J., Murphy K., Vierra M.A., Genovese M.C., Wardlaw A.J., Greenberg H.B., Hodge M.R., Wu L., Butcher E.C., Campbell J.J. Expression of the chemokine receptors CCR4, CCR5, and CXCR3 by human tissue-infiltrating lymphocytes. Am. J. Pathol., 2002, Vol. 160, pp. 347-355.
10. Li J., Huston G., Swain S.L. IL-7 promotes the transition of CD4 effectors to persistent memory cells. J. Exp. Med., 2003, Vol. 198, no. 12, pp. 1807-1815.
11. McKinstry K.K., Strutt T.M., Swain S.L. Regulation of CD4+ T-cell contraction during pathogen challenge. Immunol. Rev., 2010, Vol. 236, pp. 110-124.
12. Sgambelluri F., Diani M., Altomare A., Frigerio E., Drago L., Granucci F., Banfi G., Altomare G., Reali E. A role for CCR5(+)CD4 T cells in cutaneous psoriasis and for CD103(+) CCR4(+) CD8 Teff cells in the associated systemic inflammation. J. Autoimmun., 2016, Vol. 70, pp. 80-90.
13. Torres-Alvarez B., Castanedo-Cazares J.P., Fuentes-Ahumada C., Moncada B. The effect of methotrexate on the expression of cell adhesion molecules and activation molecule CD69 in psoriasis. J. Eur. Acad. Dermatol. Venereol., 2007, Vol. 21, no. 3, pp.334-339.
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For citations:
Kolerova A.V., Mikailova D.A., Beimanova M.A., Blinova E.A. CHARACTERIZATION OF CENTRAL AND EFFECTOR CD4⁺ MEMORY CELLS IN PSORIASIS. Medical Immunology (Russia). 2021;23(4):969-974. https://doi.org/10.15789/1563-0625-COC-2288