title: CD38 identifies a hypo-proliferative IL-13-secreting CD4+ T-cell subset that does not fit into existing naive and memory phenotype paradigms.
abstract: CD38 is commonly regarded as an activation marker for human T cells. Herein, we show that CD38 expression identifies a hypo-proliferative CD4(+) T-cell subset that, following TCR stimulation, retains expression of naive cell surface markers including CD45RA, CD62L and CCR7. Hypo-proliferation was mediated by reduced CD25 up-regulation upon TCR stimulation compared to CD4(+) CD38(-) cells and lack of responsiveness to exogenous IL-2. Instead, CD4(+) CD38(+) T cells expressed CD127, and hypo-proliferation was reversed by addition of IL-7, further associated with increased STAT5 phosphorylation. This phenotype was exacerbated by addition of an agonistic CD38-binding antibody, suggesting that signaling through CD38 promotes this cell profile. Activated CD4(+) CD38(+) cells had a bias towards IL-13 secretion, but not other Th2 cytokines such as IL-4 or IL-5. In comparison, the CD4(+) CD38(-) cells had a clear bias towards secretion of Th1-associated cytokines IFN-γ and TNF. The existence of such CD4(+) CD38(+) T cells may play an important role in pathologies such as asthma, which are associated with IL-13, but not IL-4 and IL-5. Coupled with responsiveness to IL-7 but not IL-2, and the involvement of CD38 ligation, our results highlight a unique T-cell subpopulation that does not fit into existing naive and memory cell paradigms.
authors.affiliation: Vaccine and Infectious Diseases Laboratory, Department Immunology, Monash University, Victoria, Australia.
authors.forename: Karen
authors.initials: K
authors.lastname: Scalzo-Inguanti
authors.forename: Magdalena
authors.initials: M
authors.lastname: Plebanski
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000819:agonists / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000378:metabolism; D018793:Interleukin-13 / Q000276:immunology / Q000378:metabolism*; D007376:Interleukin-2 / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics; D015851:Interleukin-7 / Q000378:metabolism; D053699:Interleukin-7 Receptor alpha Subunit / Q000235:genetics / Q000378:metabolism; D019041:L-Selectin / Q000235:genetics / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000235:genetics / Q000378:metabolism; D008213:Lymphocyte Activation; D010766:Phosphorylation; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D054400:Receptors, CCR7 / Q000235:genetics; D050799:STAT5 Transcription Factor / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C515370:CCR7 protein, human; D018793:Interleukin-13; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D015851:Interleukin-7; D053699:Interleukin-7 Receptor alpha Subunit; D011948:Receptors, Antigen, T-Cell; D054400:Receptors, CCR7; D050799:STAT5 Transcription Factor; D014409:Tumor Necrosis Factor-alpha; D019041:L-Selectin; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens; D051997:ADP-ribosyl Cyclase 1