Development and function of T cells in mice rendered interleukin-2 deficient by gene targeting.
Interleukin-2 (IL-2) is a lymphocytotropic hormone which is thought to have a key role in the immune response of mammalian cells. It is produced by a subpopulation of activated T-lymphocytes and acts in vitro as the principal auto- and paracrine T-cell growth factor (for reviews see refs 1-3). IL-2 is, however, not the sole T-cell growth factor, nor does it act exclusively on T cells, also promoting growth of NK cells and differentiation of B cells. A role for IL-2 in T-cell development has been postulated but remains controversial. Here we test the requirement for IL-2 in vivo using IL-2-deficient mice generated by targeted recombination. We find that mice homozygous for the IL-2 gene mutation are normal with regard to thymocyte and peripheral T-cell subset composition, but that a dysregulation of the immune system is manifested by reduced polyclonal in vitro T-cell responses and by dramatic changes in the isotype levels of serum immunoglobulins.
Schorle
H
H
Institute of Virology and Immunobiology, University of Würzburg, Germany.
Holtschke
T
T
Hünig
T
T
Schimpl
A
A
Horak
I
I
D000818:Animals; D000917:Antibody Formation; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens; D002454:Cell Differentiation; D004252:DNA Mutational Analysis; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis; D007376:Interleukin-2 / Q000172:deficiency* / Q000235:genetics; D008198:Lymph Nodes / Q000166:cytology; D008213:Lymphocyte Activation; D051379:Mice; D016176:T-Lymphocyte Subsets / Q000502:physiology; D013601:T-Lymphocytes / Q000502:physiology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology
D000945:Antigens, Differentiation, T-Lymphocyte; D015704:CD4 Antigens; D016827:CD8 Antigens; D007132:Immunoglobulin Isotypes; D007376:Interleukin-2