Increased proliferative capacity of CD4+ and CD8+ T lymphocytes from mutant sphha/sphha mice is associated with increased IL-2 receptor expression.
We previously discovered that mutant anemic mice (sphha/sphha) show increased numbers of cycling lymph node T lymphocytes when analyzed by pulse and continuous infusion of tritiated thymidine. We have now further analyzed this in vivo phenomenon by evaluating the in vitro proliferative response of anti-CD3 activated lymphocytes from anemic mice using flow cytometric cell cycle analysis with 5'-bromodeoxyuridine and Hoechst dye. We determined that sorted CD4+ and CD8+ T lymphocytes from anemic mice have significantly greater proliferative capacity when compared with syngeneic control (+/+) mice (P < 0.001). In order to explain this increased growth capacity, we examined whether these cells exhibit differences in cell-surface phenotype (Pgp-1 and IL-2 receptor expression), activation state, or transmembrane signaling, or alterations in accessory cells or cytokines. Increased proliferation of T cells from anemic mice was associated with a larger percentage of T cells expressing IL-2R (p55 or CD25) at 24 and 48 hr after activation. Increased proliferative capacity was not associated with differences in activation state, Pgp-1 phenotype, transmembrane signaling, accessory cells, or cytokines. The mechanism for the abnormally high proliferative rate of T cells from anemic mice remains unclear, but we suggest that this mutant mouse may provide an important model for further studies on the molecular basis of T-cell replication.
Maggio-Price
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L
Department of Comparative Medicine, University of Washington, Seattle 98195.
Grossmann
A
A
Shiota
F
F
Engel
D
D
D000745:Anemia, Hemolytic, Congenital / Q000503:physiopathology*; D000818:Animals; D000938:Antigen-Presenting Cells / Q000378:metabolism; D017252:CD3 Complex / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016827:CD8 Antigens / Q000032:analysis*; D002118:Calcium / Q000378:metabolism; D005260:Female; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000502:physiology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains / Q000276:immunology*; D012313:RNA / Q000032:analysis; D015375:Receptors, Interleukin-2 / Q000378:metabolism*; D013049:Spectrin / Q000172:deficiency; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D017252:CD3 Complex; D016827:CD8 Antigens; D008222:Lymphokines; D015375:Receptors, Interleukin-2; D013049:Spectrin; D012313:RNA; D002118:Calcium