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Recent studies have revealed that IFN-\u03b1 subtypes differ in their ability to control different viral infections. However, little is known about how IFN-\u03b1 subtypes differentially modulate immune cells to mediate these effects. This study compared the effects of IFN-\u03b12 and IFN-\u03b114, subtypes identified to differentially control viral infection, on T cells both in vivo in humanized TKO-BLT mice and in vitro using human peripheral blood mononuclear cells (PBMC). Treatment of humanized mice with the 2 IFN-\u03b1 subtypes resulted in the differential modulation of genes associated with T-cell immunity, such as proliferation, activation and inhibition. Therefore, we assessed whether stimulation of PBMC in the presence of IFN-\u03b12 or IFN-\u03b114 resulted in subtype-specific effects on T cells in vitro. IFN-\u03b114 decreased the proliferation of human CD4+ and CD8+ T cells significantly more than IFN-\u03b12. Additionally, IFN-\u03b114 increased expression of T-cell activation markers and the frequency of IL-2 producing T cells to a significantly greater extent compared to IFN-\u03b12. However, the co-culture of CD8+ T cells with IFN-\u03b1-treated, autologous CD4+ T cells or IFN-\u03b1-matured monocyte-derived dendritic cells (mo-DC) only increased the expression of CD38 compared to no IFN-\u03b1 treatment in a non-subtype specific manner. Overall, we identified IFN-\u03b1 subtype-specific effects on the proliferation and activation of T cells. However, there were no significant differences detected directly between the IFN-\u03b1 subtypes when the effects on CD8+ T cells arose through IFN-\u03b1 pre-treatment of CD4+ T cells or mo-DC.<\/jats:p>","DOI":"10.1093\/jimmun\/vkag259","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T17:16:16Z","timestamp":1790356576000},"source":"Crossref","is-referenced-by-count":0,"title":["Distinct effects of two different human interferon-alpha subtypes on indicators of T-cell proliferation, activation and inhibition"],"prefix":"10.1093","volume":"215","author":[{"given":"Madeline T H","family":"Stewart","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Microbiology and Immunology, University of Saskatchewan , Saskatoon,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunyun","family":"Di","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Microbiology and Immunology, University of Saskatchewan , Saskatoon,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noah D","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Microbiology and Immunology, University of Saskatchewan , Saskatoon,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saurav S","family":"Rout","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Microbiology and Immunology, University of Saskatchewan , Saskatoon,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulf","family":"Dittmer","sequence":"additional","affiliation":[{"name":"Institute of Virology, University Hospital Essen, University of Duisburg-Essen , Essen,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrin","family":"Sutter","sequence":"additional","affiliation":[{"name":"Institute of Virology, University Hospital Essen, 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