The functionally distinct subpopulations of human CD4+ helper/inducer T lymphocytes defined by anti-CD45R antibodies derive sequentially from a differentiation pathway that is regulated by activation-dependent post-thymic differentiation.
The CD4+ helper/inducer T cell population is comprised of functionally distinct subsets identifiable by the HB11 (anti-CD45R) mAb. We have previously shown that the cells that provide help for antibody production express the CD4+CD45R- phenotype. In contrast, CD4+ CD45R+ cells have minimal, if any, helper cell functions; rather, these cells function as inducers of Ts cell activity. The lineal relationship of these phenotypically and functionally distinct CD4+ subsets is unknown. In the present studies, we have examined the hypothesis that the CD4+ subpopulations identifiable with anti-CD45R antibodies represent "virgin" or "memory" T cells sequentially derived from a common differentiation pathway but differing in their relative maturation. When freshly purified cells were tested, CD4+ CD45R+ cells had no Th cell function. However, after in vitro activation with PHA and propagation in IL-2, CD4+CD45R+ cells acquired the ability to provide help for antibody production. Moreover, this functional acquisition by these cells was accompanied by their conversion to the CD4+CD45R- phenotype. Analyses of the activation, growth kinetics, and functional dose-response characteristics of CD4+CD45R+ and CD4+CD45R- cells demonstrated that our findings did not result from the selective growth of CD4+ CD45R- cells contaminating the CD4+CD45R+ preparations. Thus, these data demonstrate that the "helper" and "suppressor-inducer" subsets of CD4+ cells identified by anti-CD45R antibodies are not comprised of fully mature, phenotypically and functionally stable T cells. Rather, these CD4+ subsets appear to represent cells at different maturational stages of an activation-dependent, post-thymic differentiation pathway.
Clement
L T
LT
Department of Pediatrics, University of California-Los Angeles School of Medicine 90024.
Yamashita
N
N
Martin
A M
AM
D000328:Adult; D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D006801:Humans; D008213:Lymphocyte Activation; D010641:Phenotype; D006377:T-Lymphocytes, Helper-Inducer / Q000145:classification* / Q000276:immunology / Q000502:physiology; D013950:Thymus Gland / Q000166:cytology*
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte