The role of CD8⁺ T cells in asthma has not been fully discussed. The mechanisms of CD4⁺ and CD8⁺ cells in severe asthma (SA) development were compared. The microarray data (GSE31773) was downloaded from the Gene Expression Omnibus (GEO) database, including 20 samples of CD4⁺ and CD8⁺ T cells, which were collected from 8 health controls (HC), 4 non-severe asthma (NSA) and 8 SA patients. DEGs of CD4⁺ and CD8⁺ T cells in the HC vs. NSA and HC vs. SA groups were identified using the limma package in R. GO and pathway enrichment analysis of the common DEGs between the two groups were analyzed using DAVID. The interactive network of DEGs and significant modules were further explored. In CD4⁺ cells, there were 168 DEGs in HC vs. NSA group and 685 DEGs in HC vs. SA group, while for CD8⁺ T cells there were 719 DEGs in the HC vs. NSA groups and 1255 DEGs in the HC vs. SA groups. Besides, 80 common DEGs from CD4⁺ samples were enriched in the MAPKKK cascade and molecular metabolism, and 385 common DEGs of CD8⁺ T cells were significantly related with cell apoptosis and transformation. Moreover, two significant modules of DEGs in CD4⁺ were found to be involved with MPO and BPI. One module of CD8⁺ T cells containing PDHA1 and MRPL42 was identified to be related with glycolysis. In conclusion, MPO and BPI in CD4⁺, and PDHA1 and MRPL42 in CD8⁺ T cells might be used as specific biomarkers of SA progression. Therapy targeting the functions of CD4⁺ and CD8⁺ T cells may provide a novel perspective for SA treatment.