Professional memory CD4+ T lymphocytes preferentially reside and rest in the bone marrow.
CD4(+) T lymphocytes are key to immunological memory. Here we show that in the memory phase of specific immune responses, most of the memory CD4(+) T lymphocytes had relocated into the bone marrow (BM) within 3-8 weeks after their generation-a process involving integrin alpha2. Antigen-specific memory CD4(+) T lymphocytes highly expressed Ly-6C, unlike most splenic CD44(hi)CD62L(-) CD4(+) T lymphocytes. In adult mice, more than 80% of Ly-6C(hi)CD44(hi)CD62L(-) memory CD4(+) T lymphocytes were in the BM. In the BM, they associated to IL-7-expressing VCAM-1(+) stroma cells. Gene expression and proliferation were downregulated, indicating a resting state. Upon challenge with antigen, they rapidly expressed cytokines and CD154 and efficiently induced the production of high-affinity antibodies by B lymphocytes. Thus, in the memory phase of immunity, memory helper T cells are maintained in BM as resting but highly reactive cells in survival niches defined by IL-7-expressing stroma cells.
Tokoyoda
Koji
K
Deutsches Rheuma-Forschungszentrum (DRFZ), Charitéplatz 1, Berlin 10117, Germany. tokoyoda@drfz.de
Zehentmeier
Sandra
S
Hegazy
Ahmed N
AN
Albrecht
Inka
I
Grün
Joachim R
JR
Löhning
Max
M
Radbruch
Andreas
A
D000818:Animals; D000950:Antigens, Ly / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D001853:Bone Marrow / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015536:Down-Regulation / Q000276:immunology; D015870:Gene Expression; D007156:Immunologic Memory; D039421:Integrin alpha2 / Q000276:immunology; D015851:Interleukin-7 / Q000276:immunology / Q000378:metabolism; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D017154:Stromal Cells / Q000276:immunology / Q000378:metabolism
D000950:Antigens, Ly; D039421:Integrin alpha2; D015851:Interleukin-7; C494192:Ly-6C antigen, mouse