J Immunol. T\cell response. In addition, only previously hospitalised individuals showed a T\cell exhaustion profile. Finally, mixtures including IL\2 in response to S protein of endemic coronaviruses were the ones associated with SARS\CoV\2 S\specific T\cell response in pre\COVID\19 healthy donors samples. These results could have implications for protecting immunity against SARS\CoV\2 and recurrent COVID\19 and may help for the design of fresh prototypes and improving vaccine strategies. test was utilized for organizations comparisons. (Mild, em n /em ?=?18; severe, em n /em ?=?19) In relation to S\specific CD8+ T\cells, the bulk of CM CD8+ T\cell response was higher in mild compared to severe individuals (Number?3G). We observed the cytokine responsible of these variations was IL\2, which offered higher levels in MEM, CM and EM S\specific CD8+ T\cells in slight subjects (Number?3H; Number S5A), while very low levels and no variations were observed in IFN\+ and TNF\+ production (Number S5B). These results were confirmed by mixtures only including IL\2 and with no expression of the rest of the cytokines, CD107a and perforin, in the same subsets: MEM, CM and EM (Number?3I). Similar results were observed for three and four functions (Number S5C). In summary, IL\2 production in not terminally differentiated S\specific CD8+ T\cells was associated with slight disease progression in hospitalised acute SARS\CoV\2 infected individuals. 3.4. Polyfunctional N\specific CD4+ T\cell response was associated with slight disease in acute SARS\CoV\2 hospitalised individuals We also analysed in detail the quality of N\specific T\cell response. MEM and CM IL\2+ and EM TNF\+ N\specific CD4+ T Rabbit Polyclonal to B-Raf cell levels were higher in slight compared to severe individuals (Number?4A,B). We did not observe variations for the bulk of IFN\+ N\specific CD4+ T\cell response (Number S6A,B). Following a same profile of S\specific CD4+ T\cell response, mixtures including only IL\2+ and TNF\+ in MEM, CM and EM N\specific CD4+ T\cells were associated with slight disease progression (Number?4C). Besides, we AP1903 observed higher levels of mixtures with triple cytokine positive MEM, CM and EM CD4+ T\cells in slight compared to severe individuals (Number?4D). In fact, MEM N\specific response showed a higher proportion of triple and a variety of double mixtures (Number?4E), likewise a higher MEM polyfunctional index in slight compared to severe individuals (Number?4F). These results were reproduced in polyfunctionality of CM and AP1903 EM subsets with three and four functions that were also associated with slight disease progression (Number S6C). We did not observe great variations in N\specific CD8+ T\cell response relating with disease severity, only higher levels of mixtures with only IFN\+ T\cells in severe compared to slight individuals (Number S6D). Open in a separate window Number 4 Cytokine mixtures and polyfunctional N\specific CD4+ T\cell response are associated with COVID\19 progression. (A) N\specific CD4+ T\cell response considering the levels of cells generating IL\2 in the different CD4+ T\cell subsets, in slight and severe acute individuals organizations. (B) N\specific CD4+ T\cell response considering the levels of cells generating TNF\ in the different CD4+ T\cell subsets, in slight and severe acute individuals organizations. (C) N\specific CD4+ T\cell levels in the different T\cell subsets of mixtures including IL\2+ and TNF\+ cells for five (IFN\, TNF\, IL\2, CD107a and PRF) functions. (D) N\specific CD4+ T\cell levels in the different T\cell subsets of mixtures including IL\2+, TNF\+ and IFN\+ T\cells for five (IFN\, TNF\, IL\2, CD107a and PRF) functions. (E) N\specific MEM CD4 T\cell polyfunctionality pie charts. Each sector represents the proportion of N\specific CD4+ T\cells generating three (reddish), two (blue) and one (yellow) function. Arc represents the type of function (IFN\, TNF\, IL\2, CD107a and PRF) indicated in each sector. Permutation test, following a Spice version 6.0 software was used to assess differences between pie charts. (F) Polyfunctional index pub graph of N\specific MEM CD4+ polyfunctionality, for five functions. The medians with the interquartile ranges are shown. Each dot represents a patient. AP1903 ROUT method was utilised to identify and discard outliers. * em p /em ? ?0.05, ** em p /em ? ?0.01, *** em p /em ? ?0.001. MannCWhitney em U /em \test was utilized for organizations comparisons. (Mild, em n /em ?=?11; severe, em n /em ?=?11).