Early events in peripheral regulatory T cell induction via the nasal mucosa.
Nasal application of soluble Ags leads to Ag-specific suppression of systemic immune responses. This tolerance can be transferred to naive mice by CD4(+) regulatory T cells (T(R) cells) from the spleen, but little is known about the induction of mucosal T(R) cells in vivo. To investigate the induction of T(R) cells in the nose-draining cervical lymph node (CLN), CD4(+) T cells from DO11.10 OVA TCR transgenic mice were transferred to BALB/c recipients. Within 48 h after nasal OVA application, CD4(+) DO11.10 T cells in CLN, but not in the peripheral lymph node, had divided. Similarly, nonmucosal (i.m.) OVA application also induced CD4(+) DO11.10 T cells to proliferate in the draining inguinal lymph node (ILN), yet more vigorously and with different kinetics than the CD4(+) DO11.10 T cells in CLN. Functional analysis revealed that only proliferating CD4(+) DO11.10 T cells from CLN, and not ILN, could transfer tolerance to naive recipients. CD4(+) DO11.10 T cells from CLN were phenotypically similar to CD4(+) DO11.10 T cells from ILN, however, in CLN a higher percentage of CD25(+) proliferating CD4(+) DO11.10 T cells were detected compared with ILN. CD25 is not a discriminative marker for mucosal T(R) cells because both CD25(+) and CD25(-) CD4(+) DO11.10 T cells from the CLN could suppress delayed type hypersensitivity responses in adoptive transfer. These findings demonstrate that although striking similarities exist between the differentiation of T(R) and effector T cells, this does not include their function. We are the first to demonstrate that functional T(R) cells, which reside within both CD25(+) and CD25(-) subsets, can be isolated from CLN as early as 3 days after nasal OVA application.
Department of Molecular Cell Biology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands.
Wendy W J
WW
Unger
Femke
F
Hauet-Broere
Wendy
W
Jansen
Lisette A
LA
van Berkel
Georg
G
Kraal
Janneke N
JN
Samsom
D036541:ADP-ribosyl Cyclase / Q000096:biosynthesis; D051997:ADP-ribosyl Cyclase 1; D000281:Administration, Intranasal; D019264:Adoptive Transfer; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D000943:Antigens, Differentiation / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D060908:CTLA-4 Antigen; D002455:Cell Division / Q000276:immunology; D002469:Cell Separation; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000276:immunology; D005260:Female; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D007108:Immune Tolerance / Q000276:immunology; D016130:Immunophenotyping; D019041:L-Selectin / Q000096:biosynthesis; D037181:Lectins, C-Type; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008562:Membrane Glycoproteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009297:Nasal Mucosa / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D009333:Neck; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D013997:Time Factors; D000099192:CD69 Antigens
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D015703:Antigens, CD; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D060908:CTLA-4 Antigen; D016207:Cytokines; D018960:Hyaluronan Receptors; D019041:L-Selectin; D037181:Lectins, C-Type; D017493:Leukocyte Common Antigens; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D010047:Ovalbumin; D015375:Receptors, Interleukin-2; D000099192:CD69 Antigens; C556707:Ctla4 protein, mouse; C498155:Cd38 protein, mouse