CD4+CD45RA+ and CD4+CD45RA- T cell subsets in man maintain distinct function and CD45RA expression persists on a subpopulation of CD45RA+ cells after activation with Con A.
We have previously shown that Con A-induced suppressor T cells belong to the CD45RA+ subset. After unseparated T cells are activated with Con A, CD45RA expression increases to a maximum (Day 2), and then decreases significantly, but does not disappear entirely (Day 9), while CD29 expression increases steadily. In the present study, we examined the fate of these cell surface molecules on isolated CD4+CD45RA+ and CD4+CD45RA- cells following activation with Con A, and their relationship to the regulatory functions of these subsets. After activation of CD4+CD45RA+ cells with Con A, CD45RO and CD29 antigen expression rapidly increases (greater than 90%). While CD45RA expression is downregulated, approximately 40% of the cells continue to express low-density CD45RA in a stable fashion through Day 21. Despite these phenotypic changes, cells originally CD45RA+ continue to suppress IgG synthesis and provide only minimal B cell help. Furthermore, when cells originally CD45RA+ were sorted on the basis of continued presence, or loss of CD45RA antigen 14 days after activation, both populations demonstrated potent suppression and minimal help. In contrast, after activation with Con A, CD4+CD45A- cells maintain stable phenotype and provide significant help and minimal suppression. Immunoprecipitation of the CD45RA antigen from Day 14 activated CD4+CD45RA+ cells confirms the continued presence of the 205-kDa isoform, but reveals a significant decrease in the 220-kDa isoform. These results suggest that after activation with Con A, cells originally CD45RA+ remain functionally distinct from cells originally CD45RA-, and that CD45RA antigen persists on a subpopulation of CD45RA+ cells after activation with Con A.
Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115.
D M
DM
Rothstein
S
S
Sohen
J F
JF
Daley
S F
SF
Schlossman
C
C
Morimoto
D015703:Antigens, CD / Q000096:biosynthesis*; D000943:Antigens, Differentiation / Q000096:biosynthesis*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003208:Concanavalin A / Q000494:pharmacology; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D066298:In Vitro Techniques; D019012:Integrin beta1; D017493:Leukocyte Common Antigens; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008970:Molecular Weight; D010641:Phenotype; D011043:Pokeweed Mitogens / Q000494:pharmacology; D011233:Precipitin Tests; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D007074:Immunoglobulin G; D019012:Integrin beta1; D011043:Pokeweed Mitogens; D003208:Concanavalin A; D017493:Leukocyte Common Antigens