Clonal competition inhibits the proliferation and differentiation of adoptively transferred TCR transgenic CD4 T cells in response to infection.
CD4 and CD8 T cells have been shown to proliferate and differentiate to different extents following antigenic stimulation. CD4 T cells form a heterogenous pool of effector cells in various stages of division and differentiation, while nearly all responding CD8 T cells divide and differentiate to the same extent. We examined CD4 and CD8 T cell responses during bacterial infection by adoptive transfer of CFSE-labeled monoclonal and polyclonal T cells. Monoclonal and polyclonal CD8 T cells both divided extensively, whereas monoclonal CD4 T cells underwent limited division in comparison with polyclonal CD4 T cells. Titration studies revealed that the limited proliferation of transferred monoclonal CD4 T cells was due to inhibition by a high precursor frequency of clonal T cells. This unusually high precursor frequency of clonal CD4 T cells also inhibited the differentiation of these cells. These results suggest that the adoptive transfer of TCR transgenic CD4 T cells significantly underestimates the extent of proliferation and differentiation of CD4 T cells following infection.
Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Kathryn E
KE
Foulds
Hao
H
Shen
D019264:Adoptive Transfer; D000818:Animals; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology*; D049109:Cell Proliferation; D002999:Clone Cells; D008099:Liver / Q000276:immunology / Q000382:microbiology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D013154:Spleen / Q000276:immunology / Q000382:microbiology
D011948:Receptors, Antigen, T-Cell