The role of functionally distinct helper T lymphocyte subpopulations in the induction of human B cell differentiation.
Human helper T lymphocytes can be dissected into two functionally distinct subpopulations based on expression of the CD45RA (2H4) or CD45R0 (UCHL-1) surface antigens. While both subpopulations are able to induce equivalent levels of B cell activation and proliferation, only the CD4+CD45RA- subpopulation is capable of inducing B cell differentiation in pokeweed mitogen (PWM)-stimulated cultures. To define the mechanism responsible for the dichotomy between induction of proliferation and differentiation by the two CD4+ subpopulations, we examined the abilities of the purified T cell subpopulations to produce lymphokine mRNA following T cell activation. Northern analysis revealed that both subpopulations produced interleukin (IL) 2 and interferon (IFN)-gamma mRNA following PWM activation. The CD4+CD45RA- subpopulation, however, produced higher levels of IFN-gamma mRNA and the CD4+CD45RA+ cells produced higher levels of IL 2 mRNA. Neither subpopulation elaborated detectable mRNA for IL 4, IL 5 or IL 6. Of greatest significance was that the addition of recombinant or T cell-derived lymphokines could not compensate for the inability of the CD4+CD45RA+ subpopulation to induce B cell differentiation in PWM assays. Direct T-B cell contact was required for the optimal induction B cell differentiation in these assays, suggesting that CD4+CD45RA+ T cells were deficient in their ability to directly deliver the T cell-B cell signals required for B cell differentiation. These results suggest that the differential ability of the two subpopulations of CD4+ T cells to induce B cell differentiation does not result from differences in lymphokines elaborated, but may result from differences in their abilities to interact directly with B cells to initiate differentiation.
Sleasman
J W
JW
Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA 02115.
Morimoto
C
C
Schlossman
S F
SF
Tedder
T F
TF
D015703:Antigens, CD / Q000502:physiology; D000943:Antigens, Differentiation / Q000502:physiology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D001685:Biological Factors / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D016207:Cytokines; D006649:Histocompatibility Antigens / Q000502:physiology; D006801:Humans; D017493:Leukocyte Common Antigens; D008222:Lymphokines / Q000235:genetics; D011043:Pokeweed Mitogens / Q000494:pharmacology; D011061:Poly A / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D001685:Biological Factors; D016207:Cytokines; D006649:Histocompatibility Antigens; D008222:Lymphokines; D011043:Pokeweed Mitogens; D012333:RNA, Messenger; D011994:Recombinant Proteins; D011061:Poly A; D017493:Leukocyte Common Antigens