Proliferative and regenerative capacities of CD4(+) T cells upon TCR stimulation.
Proliferation of activated CD4(+) T cells effectively amplifies the immune response. Based on a model of selective CD4(+) T cell proliferation using an anti-CD3:anti-CD8 bispecific monoclonal antibody that leads to selective proliferation of CD4(+) T cells, we demonstrated that the peripheral CD4(+) T cells of normal subjects can divide for 17 to 38 generations, expanding 1.7 x 10(5) to 3 x 10(11) fold, following a single short period of anti-TCR stimulation. The proliferating CD4(+) T cells maintained IL2R expression. A large subgroup from each subject maintained the CD45RA(hi)CD45RO(lo) phenotype, demonstrating that activation and proliferation do not automatically convert CD4(+) T cells into CD45RA(lo)CD45RO(hi) phenotype. The enormous number of cells generated demonstrated that the peripheral CD4(+) T cells have remarkable regenerative expansion capacity. The high, but substantially variable, proliferative capacities among subjects have important implications for diseases in which CD4(+) T cells play an important role, such as HIV-infection, graft rejection, and autoimmunity.
Liu
Z
Z
Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, 02114, USA.
Wong
J T
JT
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000502:physiology; D002455:Cell Division; D004396:Coloring Agents; D005260:Female; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006801:Humans; D016130:Immunophenotyping; D017493:Leukocyte Common Antigens; D008297:Male; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D012038:Regeneration; D013997:Time Factors
D004396:Coloring Agents; D006684:HLA-DR Antigens; D011948:Receptors, Antigen, T-Cell; D017493:Leukocyte Common Antigens