Survival of naive CD4 T cells: roles of restricting versus selecting MHC class II and cytokine milieu.
The diversity of naive CD4 T cells plays an important role in the adaptive immune response by ensuring the capability of responding to novel pathogens. In the past, it has been generally accepted that naive CD4 T cells are intrinsically long-lived; however, there have been studies suggesting some CD4 T cells are short-lived. In this report, we identify two populations of naive CD4 T cells: a long-lived population as well as a short-lived population. In addition, we identify two factors that contribute to the establishment of long-lived naive CD4 T cells. We confirm earlier findings that MHC class II interaction with the TCR on CD4 T cells is important for survival. Furthermore, we find that MHC class II alleles with the correct restriction element for Ag presentation mediate the peripheral survival of naive CD4 T cells more efficiently than other positively selecting alleles, regardless of the selecting MHC in the thymus. The second component contributing to the survival of naive CD4 T cells is contact with the cytokines IL-4 and IL-7. We find that the physiological levels of IL-4 and IL-7 serve to enhance the MHC class II-mediated survival of naive CD4 T cells in vivo.
Boursalian
T E
TE
Section of Immunobiology, Yale University School of Medicine, Howard Hughes Medical Institute, New Haven, CT 06520, USA.
Bottomly
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D000276:Adjuvants, Immunologic / Q000502:physiology; D000818:Animals; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D002470:Cell Survival / Q000276:immunology; D017637:Clonal Deletion; D016207:Cytokines / Q000502:physiology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000502:physiology*; D015847:Interleukin-4 / Q000502:physiology; D015851:Interleukin-7 / Q000502:physiology; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010455:Peptides / Q000276:immunology / Q000378:metabolism; D013934:Thymectomy
D000276:Adjuvants, Immunologic; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D015851:Interleukin-7; D010455:Peptides; D015847:Interleukin-4