T-cell colony formation in patients with T-cell malignancies: growth factor requirements for in-vitro proliferation of peripheral blood T-cell colony-forming cells.
Peripheral blood T colony-forming cells (T-CFC) from patients with T-cell malignancies are capable of proliferation in methylcellulose, in the absence of added growth factors or mitogenic stimulation. We show here that based on the spontaneous plating efficiencies of their T-CFC, two groups of patients can be established: Group A (10 patients) with a high colony number (more than 100 colonies/10(5) seeded cells), and group B (12 patients) with less than 100 colonies/10(5) cells. The addition of interleukin 2-(IL2) containing PHA-leukocyte conditioned medium enhanced colony growth from group B but not group A patients. Moreover, both biochemically purified and recombinant IL2 induced the colony growth from group B but not group A patients without any other stimulation. In addition, a monoclonal antibody (moAb) against the IL2 receptor (IL2-R; anti-Tac) inhibited the spontaneous colony formation from T-CFC of both groups of patients. These observations strongly suggest that IL2-R are involved in the spontaneous colony growth of T-CFC. To determine whether IL2 is also involved in the spontaneous colony formation, media conditioned (LCM) by unstimulated leukemic cells were tested for IL2 activity. A constitutive release of IL2 was detected in LCM from only 2 out of 10 patients tested, and some of them were capable to inhibit thymidine incorporation by IL2-dependent cells cultured in the presence of highly purified IL2. However, most of these LCM contained a T-cell colony-promoting activity (TCPA) inducing colony formation from both normal resting and PHA-stimulated E+ clonogenic cells without added IL2 or mitogenic stimulation. TCPA-containing LCM induced the expression of functional IL2-R and IL2 release by normal resting lymphocytes. TCPA was constitutively released by blast-enriched cell fractions suggesting that it is released by the leukemic cells.
D000911:Antibodies, Monoclonal / Q000276:immunology; D000954:Antigens, Surface / Q000276:immunology; D003115:Colony-Stimulating Factors / Q000032:analysis; D003470:Culture Media; D006133:Growth Substances / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000502:physiology; D007376:Interleukin-2 / Q000502:physiology; D007945:Leukemia, Lymphoid / Q000473:pathology*; D008213:Lymphocyte Activation; D008223:Lymphoma / Q000473:pathology*; D011971:Receptors, Immunologic / Q000502:physiology; D015375:Receptors, Interleukin-2; D013601:T-Lymphocytes / Q000473:pathology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D003115:Colony-Stimulating Factors; D003470:Culture Media; D006133:Growth Substances; D007375:Interleukin-1; D007376:Interleukin-2; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7