High-frequency and adaptive-like dynamics of human CD1 self-reactive T cells.
CD1 molecules present lipid antigens to T cells. An intriguing subset of human T cells recognize CD1-expressing cells without deliberately added lipids. Frequency, subset distribution, clonal composition, naïve-to-memory dynamic transition of these CD1 self-reactive T cells remain largely unknown. By screening libraries of T-cell clones, generated from CD4(+) or CD4(-) CD8(-) double negative (DN) T cells sorted from the same donors, and by limiting dilution analysis, we find that the frequency of CD1 self-reactive T cells is unexpectedly high in both T-cell subsets, in the range of 1/10-1/300 circulating T cells. These T cells predominantly recognize CD1a and CD1c and express diverse TCRs. Frequency comparisons of T-cell clones from sorted naïve and memory compartments of umbilical cord and adult blood show that CD1 self-reactive T cells are naïve at birth and undergo an age-dependent increase in the memory compartment, suggesting a naïve/memory adaptive-like population dynamics. CD1 self-reactive clones exhibit mostly Th1 and Th0 functional activities, depending on the subset and on the CD1 isotype restriction. These findings unveil the unanticipated relevance of self-lipid T-cell response in humans and clarify the basic parameters of the lipid-specific T-cell physiology.
Experimental Immunology Unit, Division of Immunology, Transplantation and Infectious Diseases, DIBIT, San Raffaele Scientific Institute, Milano, Italy.
Claudia
C
de Lalla
Marco
M
Lepore
Francesco M
FM
Piccolo
Anna
A
Rinaldi
Andrea
A
Scelfo
Claudio
C
Garavaglia
Lucia
L
Mori
Gennaro
G
De Libero
Paolo
P
Dellabona
Giulia
G
Casorati
D056704:Adaptive Immunity; D000328:Adult; D017951:Antigen Presentation; D018949:Antigens, CD1 / Q000378:metabolism*; D001324:Autoantigens; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D007156:Immunologic Memory; D066298:In Vitro Techniques; D007231:Infant, Newborn; D008055:Lipids / Q000276:immunology; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*
D018949:Antigens, CD1; D001324:Autoantigens; D008055:Lipids; D011948:Receptors, Antigen, T-Cell