IL-7Rαlow memory CD8+ T cells are significantly elevated in patients with systemic lupus erythematosus.
OBJECTIVE
Human effector memory (EM) CD8(+) T cells include IL-7Rα(high) and IL-7Rα(low) cells with distinct cellular characteristics, including the expression of cytotoxic molecules. Both NK cells and the NK cell-associated molecule 2B4 that is expressed on CD8(+) T cells promote cytotoxicity. Here we analysed the expression of 2B4 on IL-7Rα(high) and IL-7Rα(low) EM CD8(+) T cells and its contribution to cytotoxicity. We also analysed the frequency of IL-7Rα(high) and IL-7Rα(low) EM CD8(+) T cells in patients with SLE or lupus and in healthy individuals given the potential role of cytotoxic CD8(+) T cells in the pathogenesis of lupus.


METHODS
We used flow cytometry to measure the expression of 2B4 on IL-7Rα(high) and IL-7Rα(low) EM CD8(+) T cells as well as the frequency of these cell populations in the peripheral blood of healthy individuals and patients with SLE. Also, 2B4-mediated cytotoxicity was quantitated in IL-7Rα(high) and IL-7Rα(low) EM CD8(+) T cells using target cells with CD48 antigen.


RESULTS
We found that IL-7Rα(high) EM CD8(+) T cells had higher levels of 2B4 expression compared with IL-7Rα(low) EM CD8(+) T cells. Triggering 2B4 enhanced the cytotoxic function of IL-7Rα(low) EM CD8(+) T cells against target cells. We also noticed that patients with SLE had an increased frequency of IL-7Rα(low) EM CD8(+) T cells that correlated with disease manifestation.


CONCLUSIONS
Our findings show that SLE patients have increased IL-7Rα(low) EM CD8(+) T cells, possibly contributing to tissue damage through 2B4-mediated cytotoxicity.
Department of Anatomy, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, Republic of Korea.
Jung-Sik
JS
Kim
Bon-A
BA
Cho
Ji Hyun
JH
Sim
Kamini
K
Shah
Connie M
CM
Woo
Eun Bong
EB
Lee
Dong-Sup
DS
Lee
Jae Seung
JS
Kang
Wang Jae
WJ
Lee
Chung-Gyu
CG
Park
Joe
J
Craft
Insoo
I
Kang
Hang-Rae
HR
Kim
D000328:Adult; D019138:Antibodies, Blocking / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D016130:Immunophenotyping; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology*; D018655:Lymphocyte Count; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism*; D020395:Receptors, Interleukin-7 / Q000276:immunology* / Q000378:metabolism; D000071176:Signaling Lymphocytic Activation Molecule Family
D019138:Antibodies, Blocking; D015703:Antigens, CD; C084093:CD244 protein, human; D011971:Receptors, Immunologic; D020395:Receptors, Interleukin-7; D000071176:Signaling Lymphocytic Activation Molecule Family; C415350:interleukin-7 receptor, alpha chain