AsialoGM1+CD8+ central memory-type T cells in unimmunized mice as novel immunomodulator of IFN-gamma-dependent type 1 immunity.
In unimmunized specific pathogen-free mice, there are unique memory-type CD8(+) T cell populations expressing asialoGM1 (ASGM1). These cells were classified into central memory-type T cells (T(CMT)) judging from their expression profile of CD44, IL-2Rbeta, CD62L and CCR7 cell-surface molecules. Among CD44(high)CD8(+) so-called memory CD8(+) T cell population, ASGM1(+)CD44(high)CD8(+) T(CMT), but not ASGM1(-)CD44(high)CD8(+) memory T cells, produced IFN-gamma by stimulation with anti-CD3 mAb. The physiological significance of ASGM1(+)CD8(+) T(CMT) as early source of IFN-gamma was also demonstrated in vivo. Namely, intravenous injection of anti-CD3 mAb (2 microg) resulted in early activation of IFN-gamma-producing ASGM1(+)CD8(+) T(CMT) cells as well as NKT and NK cells. Unexpectedly, however, few IFN-gamma-producing CD4(+) T cells were detected until 4 h after anti-CD3 mAb administration. Thus, ASGM1(+)CD8(+) T(CMT) were demonstrated to be early IFN-gamma producer, which may be crucial for T(h)1-dependent cellular immunity. Indeed, co-culture of naive CD4(+) T cells with ASGM1(+)CD8(+) T(CMT) but not ASGM1(-)CD8(+) T cells caused a great acceleration of IFN-gamma-producing T(h)1 cells in vitro. Finally, we found that T(h)1-prone C57BL/6 mice possessed higher percentage (10%) of ASGM1(+)CD8(+) T(CMT) in CD8(+) T cells compared with that (3%) of T(h)2-prone BALB/c mice. Moreover, ASGM1(+)CD8(+) T(CMT) derived from C57BL/6 mice produced higher levels of IFN-gamma compared with those from BALB/c mice. Thus, ASGM1(+)CD8(+) T(CMT), whose differentiation in vivo is genetically controlled, appear to play a critical role in the control of type 1 immunity, which is essential for therapy of tumors and infectious diseases.
Kosaka
Akemi
A
Division of Immunoregulation, Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan.
Wakita
Daiko
D
Matsubara
Naoki
N
Togashi
Yuji
Y
Nishimura
Shin-Ichiro
S
Kitamura
Hidemitsu
H
Nishimura
Takashi
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017252:CD3 Complex / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D018920:Coculture Techniques; D005260:Female; D005434:Flow Cytometry; D005677:G(M1) Ganglioside / Q000032:analysis*; D018960:Hyaluronan Receptors / Q000032:analysis; D007156:Immunologic Memory / Q000187:drug effects; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000172:deficiency* / Q000235:genetics; D053646:Interleukin-2 Receptor beta Subunit / Q000032:analysis; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D019041:L-Selectin / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000032:analysis; D013047:Specific Pathogen-Free Organisms; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; C515371:Ccr7 protein, mouse; C476399:Cd44 protein, mouse; D018960:Hyaluronan Receptors; C508022:Il2rb protein, mouse; D053646:Interleukin-2 Receptor beta Subunit; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D019041:L-Selectin; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside; D007371:Interferon-gamma